To see the other types of publications on this topic, follow the link: Polyamine spermidine.
Journal articles on the topic 'Polyamine spermidine'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Polyamine spermidine.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Amana, Koei H., and Shigeru Matsuzaki. "Polyamines and their biosynthetic activities in nonphytopathogenic marine agrobacteria." Canadian Journal of Microbiology 36, no. 8 (August 1, 1990): 567–72. http://dx.doi.org/10.1139/m90-099.
Full textAbstract:
Eight strains of nonphytopathogenic agrobacteria, whose taxonomic positions are uncertain, were analyzed for their polyamine contents and their polyamine biosynthetic activities. They were separated into five types on the basis of polyamine distribution patterns. The first group contains putrescine, cadaverine, and spermidine as major polyamines, the second spermidine alone, the third cadaverine alone, the fourth putrescine, spermidine, spermine, homospermidine, and aminopropyl-homospermidine, and the last contains trace amounts of diaminopropane and spermidine. These polyamine patterns of eight species seem to suggest no close phylogenic relationship among these agrobacteria and are different from those of other typical, phytopathogenic species belonging to Agrobacterium. Key words: agrobacteria, decarboxylases, polyamines, homospermidine, aminopropylhomospermidine.
2
Chibucos, M. Constantine, and Paul F. Morris. "Levels of Polyamines and Kinetic Characterization of Their Uptake in the Soybean Pathogen Phytophthora sojae." Applied and Environmental Microbiology 72, no. 5 (May 2006): 3350–56. http://dx.doi.org/10.1128/aem.72.5.3350-3356.2006.
Full textAbstract:
ABSTRACT Polyamines are ubiquitous biologically active aliphatic cations that are at least transiently available in the soil from decaying organic matter. Our objectives in this study were to characterize polyamine uptake kinetics in Phytophthora sojae zoospores and to quantify endogenous polyamines in hyphae, zoospores, and soybean roots. Zoospores contained 10 times more free putrescine than spermidine, while hyphae contained only 4 times as much free putrescine as spermidine. Zoospores contained no conjugated putrescine, but conjugated spermidine was present. Hyphae contained both conjugated putrescine and spermidine at levels comparable to the hyphal free putrescine and spermidine levels. In soybean roots, cadaverine was the most abundant polyamine, but only putrescine efflux was detected. The selective efflux of putrescine suggests that the regulation of polyamine availability is part of the overall plant strategy to influence microbial growth in the rhizosphere. In zoospores, uptake experiments with [1,4-14C]putrescine and [1,4-14C]spermidine confirmed the existence of high-affinity polyamine transport for both polyamines. Putrescine uptake was reduced by high levels of exogenous spermidine, but spermidine uptake was not reduced by exogenous putrescine. These observations suggest that P. sojae zoospores express at least two high-affinity polyamine transporters, one that is spermidine specific and a second that is putrescine specific or putrescine preferential. Disruption of polyamine uptake or metabolism has major effects on a wide range of cellular activities in other organisms and has been proposed as a potential control strategy for Phytophthora. Inhibition of polyamine uptake may be a means of reducing the fitness of the zoospore along with subsequent developmental stages that precede infection.
3
Hamana, Koei, and Shigeru Matsuzaki. "Polyamine distribution patterns serve as a phenotypic marker in the chemotaxonomy of the Proteobacteria." Canadian Journal of Microbiology 39, no. 3 (March 1, 1993): 304–10. http://dx.doi.org/10.1139/m93-043.
Full textAbstract:
Polyamines of various genera of the class Proteobacteria were analyzed by high-performance liquid chromatography to determine if they can serve as taxonomic markers. The major polyamine of Zymomonas was homospermidine, whereas the Acetobacter–Gluconobacter complex contained spermidine, suggesting the presence of two different polyamine distribution patterns in the alpha subclass. Both the homospermidine-dominant type and the spermidine-dominant type were found in heterogeneous Sphingomonas species. Typical species belonging to the gamma subclass have their own unique polyamine pattern in Xanthomonas (spermidine), Azomonas (putrescine), Frateuria (spermidine), Alteromonas (putrescine–spermidine or spermidine), Shewanella (putrescine), Marinomonas (putrescine–spermidine or spermidine), Halomonas (putrescine–spermidine or spermidine), and Deleya (spermidine). Cadaverine was sporadically distributed in some species in these genera. Some strains classified into Rhizobacter, Zoogloea, Azomonas, or Alteromonas contained 2-hydroxyputrescine found exclusively in the beta subclass. Polyamine distribution patterns are genus- and (or) species-specific and can serve as a phenotypic marker in the chemotaxonomy of the Proteobacteria.Key words: polyamine, chemotaxonomy, Proteobacteria.
4
Madeo, Frank, Sebastian J. Hofer, Tobias Pendl, Maria A. Bauer, Tobias Eisenberg, Didac Carmona-Gutierrez, and Guido Kroemer. "Nutritional Aspects of Spermidine." Annual Review of Nutrition 40, no. 1 (September 23, 2020): 135–59. http://dx.doi.org/10.1146/annurev-nutr-120419-015419.
Full textAbstract:
Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type–specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines.
5
Davis, Rohan A., Daniela Vullo, Claudiu T. Supuran, and Sally-Ann Poulsen. "Natural Product Polyamines That Inhibit Human Carbonic Anhydrases." BioMed Research International 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/374079.
Full textAbstract:
Natural product compound collections have proven an effective way to access chemical diversity and recent findings have identified phenolic, coumarin, and polyamine natural products as atypical chemotypes that inhibit carbonic anhydrases (CAs). CA enzymes are implicated as targets of variable drug therapeutic classes and the discovery of selective, drug-like CA inhibitors is essential. Just two natural product polyamines, spermine and spermidine, have until now been investigated as CA inhibitors. In this study, five more complex natural product polyamines1–5, derived from either marine sponge or fungi, were considered for inhibition of six different human CA isozymes of interest in therapeutic drug development. All compounds share a simple polyamine core fragment, either spermine or spermidine, yet display substantially different structure activity relationships for CA inhibition. Notably, polyamines1–5were submicromolar inhibitors of the cancer drug target CA IX, this is more potent than either spermine or spermidine.
6
Kramer, George F., Chien Yi Wang, and William S. Conway. "Inhibition of Softening by Polyamine Application in `Golden Delicious' and `McIntosh' Apples." Journal of the American Society for Horticultural Science 116, no. 5 (September 1991): 813–17. http://dx.doi.org/10.21273/jashs.116.5.813.
Full textAbstract:
Pressure infiltration of `Golden Delicious' and `McIntosh' apples (Malus domestica Borkh.) with polyamides resulted in an immediate increase in firmness. `Golden Delicious' apples were 2.7 N (0.25 mM spermidine) to 6.7 N (1.0 mM spermine) firmer, while `McIntosh' apples were 2.2 N (0.25 mM spermidine) to 5.3 N (1.0 mM spermine) firmer than the water-treated control. During 28 weeks of storage at 0C, the differences between the polyamine-treated and water-treated apples were even larger. Similar results were observed with a 3% Ca treatment, but the Ca treatment reduced the rate of softening to a greater extent than did the polyamine treatments in `Golden Delicious'. Polyamides increased the endogenous levels of the polyamides infiltrated; however, the levels declined rapidly with time in storage. Both polyamine and Ca inhibited the development of chilling injury symptoms (brown core) in `McIntosh'. The influence of polyamines on ethylene production was negligible in both cultivars. The Ca treatment, however, inhibited ethylene evolution in `Golden Delicious'. Polyamides, thus, may affect apple softening through rigidification of cell walls rather than through interactions with ethylene metabolism.
7
Murray-Stewart, Tracy, Matthew Dunworth, Jackson Foley, Charles Schwartz, and Robert Casero. "Polyamine Homeostasis in Snyder-Robinson Syndrome." Medical Sciences 6, no. 4 (December 7, 2018): 112. http://dx.doi.org/10.3390/medsci6040112.
Full textAbstract:
Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.
8
Olle, H. "Putrescine, Spermidine, and Spermine." Physiology 1, no. 1 (February 1, 1986): 12–15. http://dx.doi.org/10.1152/physiologyonline.1986.1.1.12.
Full textAbstract:
Putrescine was first isolated from putrifying meat and was thought of as a decomposition product;spermine was named from its occurrence in semen. These polyamines, however, are now known to have important roles in cell growth and differentiation. Their physiological significance can be studied by analyzing the consequences of depletion of the cellular polyamine content. The results include arrest of cell growth, differentiation, and division. Further results suggest that blocking of polyamine synthesis may have broad implications in clinical medicine.
9
Erwin, B. G., and A. E. Pegg. "Regulation of spermidine/spermine N1-acetyltransferase in L6 cells by polyamines and related compounds." Biochemical Journal 238, no. 2 (September 1, 1986): 581–87. http://dx.doi.org/10.1042/bj2380581.
Full textAbstract:
Exposure of rat L6 cells in culture to exogenous polyamines led to a very large increase in the activity of spermidine/spermine N1-acetyltransferase. Spermine was more potent than spermidine in bringing about this increase, but in both cases the elevated acetyltransferase activity increased the cellular conversion of spermidine into putrescine. The N1-acetyltransferase turned over very rapidly in the L6 cells, with a half-life of 9 min after spermidine and 18 min after spermine. A wide variety of synthetic polyamine analogues also brought about a substantial induction of spermidine/spermine N1-acetyltransferase activity. These included sym-norspermidine, sym-norspermine, sym-homospermidine, N4-substituted spermidine derivatives, 1,3,6-triaminohexane, 1,4,7-triaminoheptane and deoxyspergualin, which were comparable with spermidine in their potency, and N1N8-bis(ethyl)spermidine, N1N9-bis(ethyl)homospermidine, methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone) and 1,1′-[(methylethanediylidene)dinitrilo]bis(3-amino-guanidine), which were even more active than spermidine. It is suggested that these polyamine analogues may bring about a decrease in cellular polyamines not only by inhibiting biosynthesis but by stimulating the degradation of spermidine into putrescine.
10
Morgan, D. M. L. "Oxidized polyamines and the growth of human vascular endothelial cells. Prevention of cytotoxic effects by selective acetylation." Biochemical Journal 242, no. 2 (March 1, 1987): 347–52. http://dx.doi.org/10.1042/bj2420347.
Full textAbstract:
The responses of human umbilical-vein vascular endothelial cells in culture to the naturally occurring polyamines spermine, spermidine and putrescine, their acetyl derivatives and oxidation products were examined. In the absence of human polyamine oxidase, exposure of cells to polyamines (up to 160 microM) had no adverse effects. In the presence of polyamine oxidase, spermine and spermidine were cytotoxic, but putrescine was not. Acetylation of the aminopropyl group of spermidine or both aminopropyl groups of spermine prevented this cytotoxicity. The amino acids corresponding to the polyamines, representing a further stage of oxidation, were also without effect. The cytotoxic effects were irreversible. Use of bovine serum amine oxidase in place of the human enzyme gave qualitatively similar results.
11
Hyvönen, Mervi T., Michael T. Howard, Christine B. Anderson, Nikolay Grigorenko, Alex R. Khomutov, Jouko Vepsäläinen, Leena Alhonen, Juhani Jänne, and Tuomo A. Keinänen. "Divergent regulation of the key enzymes of polyamine metabolism by chiral α-methylated polyamine analogues." Biochemical Journal 422, no. 2 (August 13, 2009): 321–28. http://dx.doi.org/10.1042/bj20090737.
Full textAbstract:
The natural polyamines are ubiquitous multifunctional organic cations which play important roles in regulating cellular proliferation and survival. Here we present a novel approach to investigating polyamine functions by using optical isomers of MeSpd (α-methylspermidine) and Me2Spm (α,ω-bismethylspermine), metabolically stable functional mimetics of natural polyamines. We studied the ability of MeSpd and Me2Spm to alter the normal polyamine regulation pathways at the level of polyamine uptake and the major control mechanisms known to affect the key polyamine metabolic enzymes. These include: (i) ODC (ornithine decarboxylase), which catalyses the rate-limiting step of polyamine synthesis; (ii) ODC antizyme, an inhibitor of ODC and polyamine uptake; (iii) SSAT (spermidine/spermine N1-acetyltransferase), the major polyamine catabolic enzyme; and (iv) AdoMetDC (S-adenosyl-L-methionine decarboxylase), which is required for the conversion of putrescine into spermidine, and spermidine into spermine. We show that the stereoisomers differ in their cellular uptake and ability to downregulate ODC and AdoMetDC, and to induce SSAT. These effects are mediated by the ability of the enantiomers to induce +1 ribosomal frameshifting on ODC antizyme mRNA, to suppress the translation of AdoMetDC uORF (upstream open reading frame) and to regulate the alternative splicing of SSAT pre-mRNA. The unique effects of chiral polyamine analogues on polyamine metabolism may offer novel possibilities for studying the physiological functions, control mechanisms, and targets of the natural polyamines, as well as advance therapeutic drug development in cancer and other human health-related issues.
12
Bogle, R. G., G. E. Mann, J. D. Pearson, and D. M. Morgan. "Endothelial polyamine uptake: selective stimulation by L-arginine deprivation or polyamine depletion." American Journal of Physiology-Cell Physiology 266, no. 3 (March 1, 1994): C776—C783. http://dx.doi.org/10.1152/ajpcell.1994.266.3.c776.
Full textAbstract:
Uptake of putrescine and spermidine by cultured porcine aortic endothelial cells was time dependent and linear for 60 min. Transport, against a 5- to 10-fold concentration gradient, demonstrated both saturable and non-saturable components. Apparent concentration giving one-half maximal transport (Kt) values for putrescine and spermidine were 9 and 0.6 microM, respectively. Transport was reduced at 0 degrees C, suggesting that the process is energy requiring; inhibition by N-ethylmaleimide or p-chloromercuribenzoate suggested a requirement for sulfydryl groups. Transport of putrescine, but not spermidine, was partially activated by Na+. Spermidine and spermine did not inhibit putrescine uptake, and putrescine and spermine did not inhibit spermidine uptake, suggesting the presence of a separate transporter for each polyamine. Pretreatment with DL-2-difluoromethy-lornithine increased the uptake of putrescine but not spermidine. The endothelial cell putrescine transporter is thus sensitive to polyamine depletion, suggesting that transport from the extracellular space may be an important source of polyamines. L-Ornithine or L-arginine were not inhibitory, indicating that polyamine and cationic amino acid transport is mediated by independent systems. The sensitivity of putrescine transport to L-arginine but not to L-ornithine deprivation suggests that intracellular levels of arginine rather than ornithine regulate polyamine metabolism and transport in these cells. Thus factors that affect arginine utilization may also influence polyamine metabolism.
13
Chang, Li, Zhiqing Li, Hao Guo, Wenchang Zhang, Weiqun Lan, Jue Wang, Guanwang Shen, Qingyou Xia, and Ping Zhao. "Function of Polyamines in Regulating Cell Cycle Progression of Cultured Silkworm Cells." Insects 12, no. 7 (July 8, 2021): 624. http://dx.doi.org/10.3390/insects12070624.
Full textAbstract:
Background: Putrescine, spermidine, and spermine are polyamines that are ubiquitously distributed in prokaryotic and eukaryotic cells, which play important roles in cell proliferation and differentiation. Methods: We investigated the expression profiles of polyamine pathway genes by qRT-PCR in different tissues of the lepidopteran silkworm. The polyamine levels in cultured silkworm cells were measured by HPLC. Spermidine and polyamine biosynthetic inhibitors were used for treating the cultured silkworm cells in order to clarify their effects on cell cycle progression. Results: We identified the anabolic and catabolic enzymes that are involved in the polyamine biosynthetic pathway in silkworm. Transcriptional expression showed at least seven genes that were expressed in different silkworm tissues. Treatments of the cultured silkworm cells with spermidine or inhibitor mixtures of DFMO and MGBG induced or inhibited the expression of cell cycle-related genes, respectively, and thus led to changed progression of the cell cycle. Conclusions: The present study is the first to identify the polyamine pathway genes and to demonstrate the roles of polyamines on cell cycle progression via regulation of the expression of cell cycle genes in silkworm.
14
Krysenko, Sergii, Nicole Okoniewski, Merle Nentwich, Arne Matthews, Moritz Bäuerle, Alina Zinser, Tobias Busche, et al. "A Second Gamma-Glutamylpolyamine Synthetase, GlnA2, Is Involved in Polyamine Catabolism in Streptomyces coelicolor." International Journal of Molecular Sciences 23, no. 7 (March 29, 2022): 3752. http://dx.doi.org/10.3390/ijms23073752.
Full textAbstract:
Streptomyces coelicolor is a soil bacterium living in a habitat with very changeable nutrient availability. This organism possesses a complex nitrogen metabolism and is able to utilize the polyamines putrescine, cadaverine, spermidine, and spermine and the monoamine ethanolamine. We demonstrated that GlnA2 (SCO2241) facilitates S. coelicolor to survive under high toxic polyamine concentrations. GlnA2 is a gamma-glutamylpolyamine synthetase, an enzyme catalyzing the first step in polyamine catabolism. The role of GlnA2 was confirmed in phenotypical studies with a glnA2 deletion mutant as well as in transcriptional and biochemical analyses. Among all GS-like enzymes in S. coelicolor, GlnA2 possesses the highest specificity towards short-chain polyamines (putrescine and cadaverine), while its functional homolog GlnA3 (SCO6962) prefers long-chain polyamines (spermidine and spermine) and GlnA4 (SCO1613) accepts only monoamines. The genome-wide RNAseq analysis in the presence of the polyamines putrescine, cadaverine, spermidine, or spermine revealed indication of the occurrence of different routes for polyamine catabolism in S. coelicolor involving GlnA2 and GlnA3. Furthermore, GlnA2 and GlnA3 are differently regulated. From our results, we can propose a complemented model of polyamine catabolism in S. coelicolor, which involves the gamma-glutamylation pathway as well as other alternative utilization pathways.
15
Nagarajan, S., B. Ganem, and A. E. Pegg. "Studies of non-metabolizable polyamines that support growth of SV-3T3 cells depleted of natural polyamines by exposure to α-difluoromethylornithine." Biochemical Journal 254, no. 2 (September 1, 1988): 373–78. http://dx.doi.org/10.1042/bj2540373.
Full textAbstract:
A number of synthetic polyamine derivatives that included five achiral gem-dimethylspermidines and two analogous tetramethylated spermines were tested for their abilities to serve as substrates for enzymes metabolizing polyamines and for their capacities to substitute for the natural polyamines in cell growth. It was found that none of the compounds were effective substrates for spermine synthase, and only one, namely 8,8-dimethylspermidine, was a substrate for spermidine/spermine N1-acetyltransferase. However, all of the spermidine derivatives and 1,1,12,12-tetramethylspermine were able to support the growth of SV-3T3 cells in which endogenous polyamine synthesis was prevented by the addition of alpha-difluoromethylornithine. These results suggest that either spermidine or spermine can support cell growth without the need for metabolic interconversion. In contrast with the result with 1,1,12,12-tetramethylspermine, 3,3,10,10-tetramethylspermine did not restore growth of polyamine-depleted SV-3T3 cells. Comparison of the properties of these derivatives may prove valuable in understanding the physiological role of polyamines.
16
Limsuwun, Kornvika, and Pamela G. Jones. "Spermidine Acetyltransferase Is Required To Prevent Spermidine Toxicity at Low Temperatures in Escherichia coli." Journal of Bacteriology 182, no. 19 (October 1, 2000): 5373–80. http://dx.doi.org/10.1128/jb.182.19.5373-5380.2000.
Full textAbstract:
ABSTRACT Polyamines are required for optimal growth in most cells; however, polyamine accumulation leads to inhibition of cellular growth. To reduce intracellular polyamine levels, spermidine is monoacetylated in both prokaryotes and eukaryotes. In Escherichia coli, thespeG gene encodes the spermidine acetyltransferase, which transfers the acetyl group to either the N-1 or N-8 position. In addition to polyamine accumulation, stress conditions, such as cold shock, cause an increase in the level of spermidine acetylation, suggesting an adaptive role for reduced polyamine levels under stressful growth conditions. The effect of spermidine accumulation on the growth of E. coli at low temperature was examined using a speG mutant. At 37°C, growth of the speGmutant was normal in the presence of 0.5 or 1 mM spermidine. However, following a shift to 7°C, the addition of 0.5 or 1 mM spermidine resulted in inhibition of cellular growth or cell lysis, respectively. Furthermore, at 7°C, spermidine accumulation resulted in a decrease in total protein synthesis accompanied by an increase in the synthesis of the major cold shock proteins CspA, CspB, and CspG. However, the addition of 50 mM Mg2+ restored growth and protein synthesis in the presence of 0.5 mM spermidine. The results indicate that the level of spermidine acetylation increases at low temperature to prevent spermidine toxicity. The data suggest that the excess spermidine replaces the ribosome-bound Mg2+, resulting in ribosome inactivation at low temperatures.
17
Porter, C. W., F. G. Berger, A. E. Pegg, B. Ganis, and R. J. Bergeron. "Regulation of ornithine decarboxylase activity by spermidine and the spermidine analogue N1N8-bis(ethyl)spermidine." Biochemical Journal 242, no. 2 (March 1, 1987): 433–40. http://dx.doi.org/10.1042/bj2420433.
Full textAbstract:
Polyamine biosynthesis in intact cells can be exquisitely controlled with exogenous polyamines through the regulation of rate-limiting biosynthetic enzymes, particularly ornithine decarboxylase (ODC). In an attempt to exploit this phenomenon as an antiproliferative strategy, certain polyamine analogues have been identified [Porter, Cavanaugh, Stolowich, Ganis, Kelly & Bergeron (1985) Cancer Res. 45, 2050-2057] which lower ODC activity in intact cells, have no direct inhibitory effects on ODC, are incapable of substituting for spermidine (SPD) in supporting cell growth, and are growth-inhibitory at micromolar concentrations. In the present study, the most effective of these analogues, N1N8-bis(ethyl)SPD (BES), is compared with SPD in its ability to regulate ODC activity in intact L1210 cells and in the mechanism(s) by which this is accomplished. With respect to time and dose-dependence of ODC suppression, both polyamines closely paralleled one another in their response curves, although BES was slightly less effective than SPD. Conditions of minimal treatment leading to near-maximal ODC suppression (70-80%) were determined and found to be 3 microM for 2 h with either SPD or BES. After such treatment, ODC activity was fully recovered within 2-4 h when cells were re-seeded in drug-free media. By assessing BES or [3H]SPD concentrations in treated and recovered cells, it was possible to deduce that an intracellular accumulation of BES or SPD equivalent to less than 6.5% of the combined cellular polyamine pool was sufficient to invoke ODC regulatory mechanisms. Decreases in ODC activity after BES or SPD treatment were closely paralleled by concomitant decreases in ODC protein. Since cellular ODC mRNA was not similarly decreased by either BES or SPD, it was concluded that translational and/or post-translational mechanisms, such as increased degradation of ODC protein or decreased translation of ODC mRNA, were probably responsible for regulation of enzyme activity. Experimental evidence indicated that neither of these mechanisms seemed to be mediated by cyclic AMP or ODC-antizyme induction. On the basis of the consistent similarities between BES and SPD in all parameters studied, it is concluded that the analogue most probably acts by the same mechanisms as SPD in regulating polyamine biosynthesis.
18
Wang, Yi, Sok Ho Kim, Ramya Natarajan, Jason E. Heindl, Eric L. Bruger, Christopher M. Waters, Anthony J. Michael, and Clay Fuqua. "Spermidine Inversely Influences Surface Interactions and Planktonic Growth in Agrobacterium tumefaciens." Journal of Bacteriology 198, no. 19 (July 11, 2016): 2682–91. http://dx.doi.org/10.1128/jb.00265-16.
Full textAbstract:
ABSTRACTIn bacteria, the functions of polyamines, small linear polycations, are poorly defined, but these metabolites can influence biofilm formation in several systems. Transposon insertions in an ornithine decarboxylase (odc) gene inAgrobacterium tumefaciens, predicted to direct synthesis of the polyamine putrescine from ornithine, resulted in elevated cellulose. Null mutants forodcgrew somewhat slowly in a polyamine-free medium but exhibited increased biofilm formation that was dependent on cellulose production. Spermidine is an essential metabolite inA. tumefaciensand is synthesized from putrescine inA. tumefaciensvia the stepwise actions of carboxyspermidine dehydrogenase (CASDH) and carboxyspermidine decarboxylase (CASDC). Exogenous addition of either putrescine or spermidine to theodcmutant returned biofilm formation to wild-type levels. Low levels of exogenous spermidine restored growth to CASDH and CASDC mutants, facilitating weak biofilm formation, but this was dampened with increasing concentrations. Norspermidine rescued growth for theodc, CASDH, and CASDC mutants but did not significantly affect their biofilm phenotypes, whereas in the wild type, it stimulated biofilm formation and depressed spermidine levels. Theodcmutant produced elevated levels of cyclic diguanylate monophosphate (c-di-GMP), exogenous polyamines modulated these levels, and expression of a c-di-GMP phosphodiesterase reversed the enhanced biofilm formation. Prior work revealed accumulation of the precursors putrescine and carboxyspermidine in the CASDH and CASDC mutants, respectively, but unexpectedly, both mutants accumulated homospermidine; here, we show that this requires a homospermidine synthase (hss) homologue.IMPORTANCEPolyamines are small, positively charged metabolites that are nearly ubiquitous in cellular life. They are often essential in eukaryotes and more variably in bacteria. Polyamines have been reported to influence the surface-attached biofilm formation of several bacteria. InAgrobacterium tumefaciens, mutants with diminished levels of the polyamine spermidine are stimulated for biofilm formation, and exogenous provision of spermidine decreases biofilm formation. Spermidine is also essential forA. tumefaciensgrowth, but the related polyamine norspermidine exogenously rescues growth and does not diminish biofilm formation, revealing that the growth requirement and biofilm control are separable. Polyamine control of biofilm formation appears to function via effects on the cellular second messenger cyclic diguanylate monophosphate, regulating the transition from a free-living to a surface-attached lifestyle.
19
Nicolet, T. G., J. L. Scemama, L. Pradayrol, C. Seva, and N. Vaysse. "Characterization of putrescine- and spermidine-transport systems of a rat pancreatic acinar tumoral cell line (AR4-2J)." Biochemical Journal 269, no. 3 (August 1, 1990): 629–32. http://dx.doi.org/10.1042/bj2690629.
Full textAbstract:
Polyamines are polycationic molecules essential for cell growth and differentiation. Recent work has focused on cell polyamine-transport systems as a way to regulate intracellular polyamine levels. In this study, we demonstrate the presence of two different active transporters for putrescine and spermidine in a rat tumoral cell line (AR4-2J). The first has a Km of 3.1 microM and a Vmax of 3.7 pmol/15 min per micrograms of DNA for putrescine and the second a Km of 0.42 microM and a Vmax of 4.7 pmol/15 min per micrograms of DNA for spermidine. Competition studies performed between the polyamines confirm the difference between these two carriers; one has an equal affinity for the three main polyamines, and the other has a lower affinity for putrescine. Amino acids do not share this transport system, which is Na(+)-independent. Choline chloride inhibits selectively and in a dose-responsive manner the uptake of putrescine without affecting that of spermidine. These data demonstrate that AR4-2J cells possess two polyamine transporters; one is specific for aminopropyl groups (spermidine and spermine), and the other is choline-sensitive, but cannot discriminate between aminobutyl (putrescine) and aminopropyl groups.
20
Hoet, Peter H. M., and Benoit Nemery. "Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions." American Journal of Physiology-Lung Cellular and Molecular Physiology 278, no. 3 (March 1, 2000): L417—L433. http://dx.doi.org/10.1152/ajplung.2000.278.3.l417.
Full textAbstract:
The natural polyamines putrescine, cadaverine, spermidine, and spermine are found in all cells. These (poly)cations exert interactions with anions, e.g., DNA and RNA. This feature represents their best-known direct physiological role in cellular functions: cell growth, division, and differentiation. The lung and, more specifically, alveolar epithelial cells appear to be endowed with a much higher polyamine uptake system than any other major organ. In the lung, the active accumulation of natural polyamines in the epithelium has been studied in various mammalian species including rat, hamster, rabbit, and human. The kinetic parameters (Michaelis-Menten constant and maximal uptake) of the uptake system are the same order of magnitude regardless of the polyamine or species studied and the in vitro system used. Also, other pulmonary cells accumulate polyamines but never to the same extent as the epithelium. Although different uptake systems exist for putrescine, spermidine, and spermine in the lung, neither the nature of the carrier protein nor the reason for its existence is known. Some pulmonary toxicological and/or pathological conditions have been related to polyamine metabolism and/or polyamine content in the lung. Polyamines possess an important intrinsic toxicity. From in vitro studies with nonpulmonary cells, it has been shown that spermidine and spermine can be metabolized to hydrogen peroxide, ammonium, and acrolein, which can all cause cellular toxicity. In hyperoxia or after ozone exposure, the increased polyamine synthesis and polyamine content of the rat lung is correlated with survival of the animals. Pulmonary hypertension induced by monocrotaline or hypoxia has also been linked to the increased polyamine metabolism and polyamine content of the lung. In a small number of studies, it has been shown that polyamines can contribute to the suppression of immunologic reactions in the lung.
21
Bjelakovic, Gordana, Dusica Pavlovic, Tatjana Jevtovic, Ivana Stojanovic, Dušan Sokolovic, Goran B. Bjelakovic, Jelenka Nikolic, and Jelena Basic. "Vitamin Β12 and Folic Acid Effects on Polyamine Metabolism in Rat Liver." Pteridines 17, no. 3 (August 2006): 90–94. http://dx.doi.org/10.1515/pteridines.2006.17.3.90.
Full textAbstract:
Abstract Polyamines, spennine, spermidine and putrescinc, small aliphatic nitrous bases, are normal constituents of microbial, plant and animal cells, where they fulfill an array of physiological roles. Metabolism of polyamines is associated with growth and differentiation of mammalian cells, spermine related to RNA and spermidine to DNA metabolism. Methyl-cobalamin, the coenzyme of methionine synthetase, catalyses the recycling of homocysteine to methionine using 5-methyltctrahydrofolate. By acceleration of methionine biosynthesis these vitamins may influence spermidine and spermine synthesis.Liver tissue is rich in polyamines and it is the place of vitamin B12 and folic acid deposition. Polyamine oxidase (PAO, EC 1.5.3) and diamino oxidase (DAO, EC 1.4.3.6) participate in the process of degradation and interconversion of spermine, spermidine and putrescinc. The idea of our work was to examine the effccts of cobalamin and folic acid on the polyamine metabolism. We have examined the amount of spermine, spermidine and putrescine in liver tissue. At the same time we have examined the activities of PAO and DAO, the catabolic enzymes of polyamine metabolism. Our result suggest that the supplementation of experimental animals with vitamin B12 alone or together with folic acid augmentais spermidine and spermine levels in rat liver, at the same time the amount of putrescine does not change. The application of vitamin cobalamin to experimental animals alone increases PAO; the supplementation of experimental animals with vitamin Β12 together with folic acid causes opposite effect - the decrease of PAO activity. DAO activity significantly decreases under the influence of cobalamin and also with cobalamin and folic acid in combination. Our experimental results indicate the importance of cobalamin and folic acid in polyamine metabolism.
22
MITCHELL, John L. A., Jennifer RUPERT, Aviva LEYSER, and Gary G. JUDD. "Mammalian cell polyamine homeostasis is altered by the radioprotector WR1065." Biochemical Journal 335, no. 2 (October 15, 1998): 329–34. http://dx.doi.org/10.1042/bj3350329.
Full textAbstract:
Mammalian cells become more susceptible to radiation-induced death and mutagenesis when restricted in their production of the natural polyamines putrescine, spermidine and spermine. The effects of polyamine deprivation are reversed by N-(2-mercaptoethyl)-1,3-diaminopropane (WR1065), a simple aminothiol that has been extensively studied for its radioprotectant properties. Because this compound and its oxidized derivative WR33278 bear some resemblance to the polyamines, it was hypothesized that radioprotection by WR1065 or its metabolites is derived, at least in part, from their ability to supplement the natural polyamines. To evaluate the ability of these aminothiol compounds to emulate polyamine function in intact cells, rat liver hepatoma (HTC) cells were treated with radioprotective doses of WR1065; the ability of this compound to affect various aspects of normal polyamine metabolism was monitored. Although cellular WR1065 was maintained at levels exceeding those of the polyamines, this aminothiol did not have any polyamine-like effect on the initial polyamine biosynthetic enzyme, ornithine decarboxylase, or on polyamine degradative reactions. On the contrary, treatment with relatively low levels of WR1065 resulted in an unexpected increase in putrescine and spermidine synthesis. WR1065 treatment enhanced the stability, and consequently the activity, of ornithine decarboxylase. This stabilization seems to result from a WR1065-induced delay in the synthesis of antizyme, a critical regulatory protein required in the feedback modulation of polyamine synthesis and transport. The increase in cellular spermidine induced by WR1065 might explain its antimutagenic properties, but is probably not a factor in protection against cell killing by radiation. This is the first evidence that compounds can be designed to control polyamine levels by targeting the activity of the regulatory protein antizyme.
23
Pegg, Anthony E. "Spermidine/spermine-N1-acetyltransferase: a key metabolic regulator." American Journal of Physiology-Endocrinology and Metabolism 294, no. 6 (June 2008): E995—E1010. http://dx.doi.org/10.1152/ajpendo.90217.2008.
Full textAbstract:
Spermidine/spermine- N1-acetyltransferase (SSAT) regulates cellular polyamine content. Its acetylated products are either excreted from the cell or oxidized by acetylpolyamine oxidase. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. SSAT is very highly regulated. Its content is adjusted in response to alterations in polyamine content to maintain polyamine homeostasis. Certain polyamine analogs can mimic the induction of SSAT and cause a loss of normal polyamines. This may have utility in cancer chemotherapy. SSAT activity is also induced via a variety of other stimuli, including toxins, hormones, cytokines, nonsteroidal anti-inflammatory agents, natural products, and stress pathways, and by ischemia-reperfusion injury. These increases are initiated by alterations in Sat1 gene transcription reinforced by alterations at the other regulatory steps, including protein turnover, mRNA processing, and translation. Transgenic manipulation of SSAT activity has revealed that SSAT activity links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. A high level of SSAT stimulates flux through the polyamine biosynthetic pathway, since biosynthetic enzymes are induced in response to the fall in polyamines. This sets up a futile cycle in which ATP is used to generate S-adenosylmethionine for polyamine biosynthesis and acetyl-CoA is consumed in the acetylation reaction. A variety of other effects of increased SSAT activity include death of pancreatic cells, blockage of regenerative tissue growth, behavioral changes, keratosis follicularis spinulosa decalvans, and hair loss. These are very likely due to changes in polyamine and putrescine levels, although increased oxidative stress via the oxidation of acetylated polyamines may also contribute. Recently, it was found that the SSAT protein and/or a related protein, thialysine acetyltransferase, interacts with a number of other important proteins, including the hypoxia-inducible factor-1 α-subunit, the p65 subunit of NF-κB, and α9β1-integrin, altering the function of these proteins. It is not yet clear whether this functional alteration involves protein acetylation, local polyamine concentration changes, or other effects. It has been suggested that SSAT may also be a useful target in diseases other than cancer, but the wide-ranging physiological and pathophysiological effects of altered SSAT expression will require very careful limitation of such strategies to the relevant cells to avoid toxic effects.
24
FRASER, Alison V., Patrick M. WOSTER, and Heather M. WALLACE. "Induction of apoptosis in human leukaemic cells by IPENSpm, a novel polyamine analogue and anti-metabolite." Biochemical Journal 367, no. 1 (October 1, 2002): 307–12. http://dx.doi.org/10.1042/bj20020156.
Full textAbstract:
Human promyelogenous leukaemic cells (HL-60) were treated with novel spermine analogue, (S)-N1-(2-methyl-1-butyl)-N11-ethyl-4,8-diazaundecane (IPENSpm), and the effects on growth and intracellular polyamine metabolism were measured. IPENSpm was cytotoxic to these cells at concentrations greater than 2.5μM. It induced apoptosis in a caspase-dependent manner and its toxicity profile was comparable with etoposide, a well-known anti-tumour agent and inducer of apoptosis. IPENSpm decreased intracellular polyamine content as a result of changes in ornithine decarboxylase activity and increases in spermidine/spermine N1-acetyltransferase and polyamine export. Analysis showed spermine and spermidine as the major intracellular polyamines, while putrescine and acetyl-polyamines were the main export compounds. IPENSpm used the polyamine transporter system for uptake and its accumulation in cells was prevented by polyamine transport inhibitors. IPENSpm can be classified as a polyamine anti-metabolite and it may be a promising new lead compound in terms of treatment of some human cancers.
25
Saunders, N. A., J. K. McGeachie, K. F. Ilett, and R. F. Minchin. "Localization of spermidine uptake in rabbit lung slices." American Journal of Physiology-Cell Physiology 257, no. 3 (September 1, 1989): C579—C587. http://dx.doi.org/10.1152/ajpcell.1989.257.3.c579.
Full textAbstract:
The lungs have a high polyamine transport capability, and the type II pneumocyte has recently been identified as a major site of putrescine uptake and localization (N. A. Saunders, P. J. Rigby, K. F. Ilett, and R. F. Minchin. Lab. Invest. 59: 380-386, 1988). However, recent evidence suggests that multiple polyamine transport systems exist. In the present study, localization of spermidine uptake in rabbit lung was investigated. Although [14C]spermidine was rapidly accumulated by lung slices, it was not significantly metabolized, and no efflux of the accumulated polyamine was apparent. Autoradiographs prepared after [3H]spermidine transport revealed a localization of uptake activity to cells identified by electron microscopy as type II pneumocytes. Spermidine uptake occurred in all type II cells examined and thus appeared to be a characteristic function of this cell type. In contrast, spermidine uptake was virtually absent in the major airways and blood vessels, whereas moderate uptake was associated with pulmonary alveolar macrophages and alveolar tissue. Subsequent purification and culture of type II pneumocytes showed these cells to have significant polyamine uptake activity. In addition, spermidine uptake activity was positively correlated with the proportion of type II cells present at the various stages of their purification. In other studies, cultured pulmonary alveolar macrophages possessed similar uptake activity to that of cultured type II cells. Combined, these data suggest that both type II cells and pulmonary alveolar macrophages may represent major sites of spermidine uptake in vivo. We also suggest that the transport of polyamines by type II cells may reflect a critical role for polyamines in a characteristic function of this cell type.
26
Byers, T. L., and A. E. Pegg. "Properties and physiological function of the polyamine transport system." American Journal of Physiology-Cell Physiology 257, no. 3 (September 1, 1989): C545—C553. http://dx.doi.org/10.1152/ajpcell.1989.257.3.c545.
Full textAbstract:
Polyamine transport was examined in Chinese hamster ovary (CHO) cells because of the unique potential these cells hold for utilizing genetic approaches to study the mechanisms of polyamine transport, its regulation, and its function. Parental (control) CHO cells were shown to contain a polyamine transport system with characteristics consistent with polyamine-uptake properties described in other cell types. Polyamines appear to cross the plasma membrane via an energy-requiring transport system specific for putrescine, spermidine, spermine, and their analogues. A mutant line, CHOMG, selected for resistance to the toxicity of methylglyoxal bis(guanylhydrazone), was shown to lack a functional polyamine transport system. CHOMG cells provided the negative controls necessary to examine the role of polyamine transport in maintenance of intracellular polyamine levels and in the regulation of the polyamine metabolic enzymes. It was found that the repression of ornithine decarboxylase activity by polyamines and the induction of spermidine/spermine-N1 acetyltransferase by polyamine analogues including bis(ethyl)spermine derivatives required the presence of a functional polyamine transport system. The CHO-CHOMG model was also shown to provide a means for establishing the importance of the polyamine transport system in the toxicity of polyamine analogues. The inability of alpha-difluoromethylornithine-treated CHOMG cells to utilize extracellular polyamines to replenish depleted intracellular polyamine levels suggested a means by which polyamine transport-positive cells may be identified. Such a selection procedure will permit the use of CHOMG cells in the isolation of genes encoding proteins involved in polyamine transport.
27
Akinyele, Oluwaseun, and Heather M. Wallace. "Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation." Biomolecules 11, no. 5 (May 17, 2021): 743. http://dx.doi.org/10.3390/biom11050743.
Full textAbstract:
Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.
28
Teixeira, Miguel C., Tânia R. Cabrito, Zaitunnissa M. Hanif, Rita C. Vargas, Sandra Tenreiro, and Isabel Sá-Correia. "Yeast response and tolerance to polyamine toxicity involving the drug : H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4." Microbiology 157, no. 4 (April 1, 2011): 945–56. http://dx.doi.org/10.1099/mic.0.043661-0.
Full textAbstract:
The yeast QDR3 gene encodes a plasma membrane drug : H+ antiporter of the DHA1 family that was described as conferring resistance against the drugs quinidine, cisplatin and bleomycin and the herbicide barban, similar to its close homologue QDR2. In this work, a new physiological role for Qdr3 in polyamine homeostasis is proposed. QDR3 is shown to confer resistance to the polyamines spermine and spermidine, but, unlike Qdr2, also a determinant of resistance to polyamines, Qdr3 has no apparent role in K+ homeostasis. QDR3 transcription is upregulated in yeast cells exposed to spermine or spermidine dependent on the transcription factors Gcn4, which controls amino acid homeostasis, and Yap1, the main regulator of oxidative stress response. Yap1 was found to be a major determinant of polyamine stress resistance in yeast and is accumulated in the nucleus of yeast cells exposed to spermidine-induced stress. QDR3 transcript levels were also found to increase under nitrogen or amino acid limitation; this regulation is also dependent on Gcn4. Consistent with the concept that Qdr3 plays a role in polyamine homeostasis, QDR3 expression was found to decrease the intracellular accumulation of [3H]spermidine, playing a role in the maintenance of the plasma membrane potential in spermidine-stressed cells.
29
Hyvönen, M. T., M. Merentie, A. Uimari, T. A. Keinänen, J. Jänne, and L. Alhonen. "Mechanisms of polyamine catabolism-induced acute pancreatitis." Biochemical Society Transactions 35, no. 2 (March 20, 2007): 326–30. http://dx.doi.org/10.1042/bst0350326.
Full textAbstract:
Acute pancreatitis is an autodigestive disease, in which the pancreatic tissue is damaged by the digestive enzymes produced by the acinar cells. Among the tissues in the mammalian body, pancreas has the highest concentration of the natural polyamine, spermidine. We have found that pancreas is very sensitive to acute decreases in the concentrations of the higher polyamines, spermidine and spermine. Activation of polyamine catabolism in transgenic rats overexpressing SSAT (spermidine/spermine-N1-acetyltransferase) in the pancreas leads to rapid depletion of these polyamines and to acute necrotizing pancreatitis. Replacement of the natural polyamines with methylated polyamine analogues before the induction of acute pancreatitis prevents the development of the disease. As premature trypsinogen activation is a common, early event leading to tissue injury in acute pancreatitis in human and in experimental animal models, we studied its role in polyamine catabolism-induced pancreatitis. Cathepsin B, a lysosomal hydrolase mediating trypsinogen activation, was activated just 2 h after induction of SSAT. Pre-treatment of the rats with bismethylspermine prevented pancreatic cathepsin B activation. Analysis of tissue ultrastructure by transmission electron microscopy revealed early dilatation of rough endoplasmic reticulum, probable disturbance of zymogen packaging, appearance of autophagosomes and later disruption of intracellular membranes and organelles. Based on these results, we suggest that rapid eradication of polyamines from cellular structures leads to premature zymogen activation and autodigestion of acinar cells.
30
SOULET, Denis, Laurence COVASSIN, Mohammadi KAOUASS, René CHAREST-GAUDREAULT, Marie AUDETTE, and Richard POULIN. "Role of endocytosis in the internalization of spermidine-C2-BODIPY, a highly fluorescent probe of polyamine transport." Biochemical Journal 367, no. 2 (October 15, 2002): 347–57. http://dx.doi.org/10.1042/bj20020764.
Full textAbstract:
The mechanism of transmembrane polyamine internalization in mammalian cells remains unknown. A novel fluorescent spermidine conjugate [Spd-C2-BODIPY; N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl)-N′-{S-[spermidine-(N4-ethyl)]thioacetyl}ethylenediamine] was synthesized from N4-(mercaptoethyl)spermidine by a simple, one-step coupling procedure. In Chinese-hamster ovary (CHO) cells, Spd-C2-BODIPY accumulation was inhibited by exogenous putrescine, spermidine and spermine, was subject to feedback transport inhibition and was up-regulated by prior polyamine depletion achieved with a biosynthetic inhibitor. Probe internalization was decreased by about 85% in a polyamine-transport-deficient CHO mutant cell line. Using confocal laser scanning fluorescence microscopy, internalized Spd-C2-BODIPY was concentrated in vesicle-like structures similar to the recycling endosomes observed with fluorescent transferrin, which partly co-localized with the polyamine probe. In yeast, Spd-C2-BODIPY uptake was stringently dependent on receptor-mediated endocytosis, as determined with a mutant defective in early- endosome formation. On the other hand, Spd-C2-BODIPY did not mimic the substrate behaviour of natural polyamines in yeast, as shown by the lack of correlation of its uptake characteristics with the phenotypes of mutants defective in either polyamine transport or biosynthesis. These data suggest that endocytosis might be an integral part of the mechanism of polyamine transport in mammalian cells, and that the mammalian and yeast transport systems use qualitatively different transport mechanisms. However, the current data do not rule out the possibility that sequestration of the probe into vesicular structures might be secondary to its prior uptake via a ‘classical’ plasma membrane carrier. Spd-C2-BODIPY, a highly sensitive probe of polyamine transport with biochemical parameters qualitatively similar to those of natural polyamines in mammalian cells, should be very useful for dissecting the pathway responsible for polyamine internalization.
31
Tajti, Hamow, Majláth, Gierczik, Németh, Janda, and Pál. "Polyamine-Induced Hormonal Changes in eds5 and sid2 Mutant Arabidopsis Plants." International Journal of Molecular Sciences 20, no. 22 (November 15, 2019): 5746. http://dx.doi.org/10.3390/ijms20225746.
Full textAbstract:
Polyamines are multifaceted compounds which play a role in regulating plant growth and stress tolerance in interactions with plant hormones. The aim of the present study was to reveal how exogenous polyamines influence the synthesis of salicylic acid, with a special emphasis on the effect of salicylic acid deficiency on the polyamine metabolism and polyamine-induced changes in other plant hormone contents. Our hypothesis was that the individual polyamines induced different changes in the polyamine and salicylic acid metabolism of the wild type and salicylic acid-deficient Arabidopsis mutants, which in turn influenced other hormones. To our knowledge, such a side-by-side comparison of the influence of eds5-1 and sid2-2 mutations on polyamines has not been reported yet. To achieve our goals, wild and mutant genotypes were tested after putrescine, spermidine or spermine treatments. Polyamine and plant hormone metabolism was investigated at metabolite and gene expression levels. Individual polyamines induced different changes in the Arabidopsis plants, and the responses were also genotype-dependent. Polyamines upregulated the polyamine synthesis and catabolism, and remarkable changes in hormone synthesis were found especially after spermidine or spermine treatments. The sid2-2 mutant showed pronounced differences compared to Col-0. Interactions between plant hormones may also be responsible for the observed differences.
32
Hyvönen, Mervi T., Olga A. Smirnova, Vladimir A. Mitkevich, Vera L. Tunitskaya, Maxim Khomutov, Dmitry S. Karpov, Sergey P. Korolev, et al. "Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions." International Journal of Molecular Sciences 23, no. 9 (April 21, 2022): 4614. http://dx.doi.org/10.3390/ijms23094614.
Full textAbstract:
The polyamines, spermine (Spm) and spermidine (Spd), are important for cell growth and function. Their homeostasis is strictly controlled, and a key downregulator of the polyamine pool is the polyamine-inducible protein, antizyme 1 (OAZ1). OAZ1 inhibits polyamine uptake and targets ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, for proteasomal degradation. Here we report, for the first time, that polyamines induce dimerization of mouse recombinant full-length OAZ1, forming an (OAZ1)2–polyamine complex. Dimerization could be modulated by functionally active C-methylated spermidine mimetics (MeSpds) by changing the position of the methyl group along the Spd backbone—2-MeSpd was a poor inducer as opposed to 1-MeSpd, 3-MeSpd, and Spd, which were good inducers. Importantly, the ability of compounds to inhibit polyamine uptake correlated with the efficiency of the (OAZ1)2–polyamine complex formation. Thus, the (OAZ1)2–polyamine complex may be needed to inhibit polyamine uptake. The efficiency of polyamine-induced ribosomal +1 frameshifting of OAZ1 mRNA could also be differentially modulated by MeSpds—2-MeSpd was a poor inducer of OAZ1 biosynthesis and hence a poor downregulator of ODC activity unlike the other MeSpds. These findings offer new insight into the OAZ1-mediated regulation of polyamine homeostasis and provide the chemical tools to study it.
33
Mendel, Ákos, László Kovács, and Erzsébet Kiss. "Effect of arginine, putrescine and spermidine on the polyamine, proline and chlorophyll content of tobacco (Nicotiana tabacum L.)." Acta Agraria Debreceniensis, no. 2 (December 8, 2021): 39–43. http://dx.doi.org/10.34101/actaagrar/2/9572.
Full textAbstract:
Polyamines, such as spermidine (Spd) spermine (Spm) and their direct precursor, the diamine putrescine (Put) are vital and essential aliphatic amines which are also present in plants. Although ethylene and polyamines are also involved in fruit ripening, the genes coding them must also take part in other biosynthetic pathways. In the ethylene and polyamines play an important role in development of salt stress tolerance, and in responses for biotic and abiotic stresses. Exogenous application of all three main polyamines (Put, Spd, Spm) increase salt tolerance of plants, but, accordingly to previous experiments, spermidine has the main effect on the enhancement of salt tolerance. Nicotiana tabacum L. plants were grown in vitro on MS medium, the treatments were as follows: arginine (150 mg l-1), putrescine (10 mg l-1), spermidine (10 mg l-1). Proline, chlorophyll a, b and polyamine contents were measured. The obtained results show that the arginine decarboxylase and the spermidine synthase genes involved in polyamine metabolism, cannot be enhanced by exogenous addition of their precursor molecules. On the contrary, the spermine synthase gene has a positive effect to the lower-class forms of polyamines.
34
Wang, J. Y., and L. R. Johnson. "Luminal polyamines stimulate repair of gastric mucosal stress ulcers." American Journal of Physiology-Gastrointestinal and Liver Physiology 259, no. 4 (October 1, 1990): G584—G592. http://dx.doi.org/10.1152/ajpgi.1990.259.4.g584.
Full textAbstract:
The purpose of this study was to examine whether luminal polyamines can substitute for tissue polyamines in the healing process of gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately or at 4, 12, or 24 h after the period of stress. Stress significantly increased ornithine decarboxylase (ODC) activity and tissue polyamine content. Mucosal polyamine levels peaked 4 h after stress and remained significantly elevated for 12 h. The healing process, which was significant by 12 h, was inhibited by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC. DFMO totally prevented the marked increases in ODC and polyamine levels that usually followed stress. Oral administration of polyamines, putrescine, cadaverine, spermidine, or spermine, immediately after stress increased the normal rate of healing and prevented the inhibition of repair caused by DFMO. Spermidine or spermine accelerated healing better than putrescine or cadaverine. The delayed recovery of mucosal DNA, RNA, and protein content after stress in the DFMO-treated rats was also significantly prevented by exogenous polyamines. The reduced amounts of gastric mucosal spermidine and spermine in rats treated with DFMO returned toward control levels after administration of exogenous spermidine (100 mg/kg). These results show that 1) increased levels of polyamines provided by ODC are absolutely required for normal healing of gastric mucosal stress ulcers, 2) the polyamines are active from the luminal side, and 3) polyamines accelerate healing at least partly through a mechanism involving cell renewal.
35
Gilroy, Caslin, Tamara Olenyik, Sigrid C. Roberts, and Buddy Ullman. "Spermidine Synthase Is Required for Virulence of Leishmania donovani." Infection and Immunity 79, no. 7 (May 2, 2011): 2764–69. http://dx.doi.org/10.1128/iai.00073-11.
Full textAbstract:
ABSTRACTGenetic lesions in the polyamine biosynthetic pathway ofLeishmania donovani, the causal agent of visceral leishmaniasis, are conditionally lethal mutations that render the insect vector form of the parasite auxotrophic for polyamines. Recently, we have demonstrated that a ΔodcL. donovaninull mutant lacking ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, was profoundly compromised in its ability to infect mice, indicating that ODC is essential for the infectious mammalian stage of the parasite and further validating the enzyme as a possible drug target. To assess whether other components of the polyamine biosynthetic pathway were also essential for parasite virulence, a cell line deficient in spermidine synthase (SPDSYN), the enzyme that converts putrescine to spermidine, was created by double-targeted gene replacement within a virulentL. donovanibackground. This Δspdsynstrain was auxotrophic for polyamines, required spermidine for growth in its insect vector form, and was adversely impacted in its ability to infect mice. These findings establish that SPDSYN, like ODC, is essential for maintaining a robust infection in mammals and indicate that pharmacologic inhibition of SPDSYN, and perhaps all components of the polyamine biosynthetic pathway, is a valid therapeutic strategy for the treatment of visceral and, potentially, other forms of leishmaniasis.
36
HELJASVAARA, Ritva, Ildiko VERESS, Maria HALMEKYTÖ, Leena ALHONEN, Juhani JÄNNE, Pasi LAAJALA, and Antti PAJUNEN. "Transgenic mice overexpressing ornithine and S-adenosylmethionine decarboxylases maintain a physiological polyamine homoeostasis in their tissues." Biochemical Journal 323, no. 2 (April 15, 1997): 457–62. http://dx.doi.org/10.1042/bj3230457.
Full textAbstract:
Recent work has shown that transgenic mice overexpressing human ornithine decarboxylase display no marked changes in the tissue concentrations of spermidine or spermine in spite of a dramatic increase in putrescine levels. In the tissues of transgenic mice carrying the human spermidine synthase gene and in those of hybrid mice overexpressing both ornithine decarboxylase and spermidine synthase, spermidine and spermine levels remain within normal limits. To test whether the amount of the propylamine group donor, decarboxylated S-adenosylmethionine, limits the conversion of putrescine into the higher polyamines, we have produced transgenic mouse lines harbouring the rat S-adenosylmethionine decarboxylase gene in their genome. However, neither these mice nor the hybrid mice overexpressing both ornithine decarboxylase and S-adenosylmethionine decarboxylase displayed significant changes in their spermidine and spermine tissue levels. To study the mechanism by which cells maintain the constancy of the polyamine concentrations, we have determined the metabolic flux of polyamines in transgenic primary fibroblasts using pulse labelling. The results indicate that the polyamine flow is faster in transgenic primary fibroblasts than in non-transgenic fibroblasts and that the intracellular homoeostasis of higher polyamines is maintained at least partly by the acetylation of spermidine and spermine and their secretion into the medium.
37
HUGHES, Alun, Nicholas I. SMITH, and Heather M. WALLACE. "Polyamines reverse non-steroidal anti-inflammatory drug-induced toxicity in human colorectal cancer cells." Biochemical Journal 374, no. 2 (September 1, 2003): 481–88. http://dx.doi.org/10.1042/bj20030280.
Full textAbstract:
Naproxen, sulindac and salicylate, three NSAIDs (non-steroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content. Inhibition of ornithine decarboxylase (the first enzyme of the polyamine biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine N1-acetyltransferase (the enzymes responsible for polyamine catabolism) and induction of polyamine export all contributed to the decreased intracellular polyamine content. Morphological examination of the cells showed typical signs of apoptosis, and this was confirmed by DNA fragmentation and measurement of caspase-3-like activity. Re-addition of spermidine to the cells partially prevented apoptosis and recovered the cell number. Thus polyamines appear to be an integral part of the signalling pathway mediating NSAID toxicity in human colorectal cancer cells, and may therefore also be important in cancer chemoprevention in humans.
38
Bacchi, Cyrus J., Donna Rattendi, Evangeline Faciane, Nigel Yarlett, Louis M. Weiss, Benjamin Frydman, Patrick Woster, Benjamin Wei, Laurence J. Marton, and Murray Wittner. "Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues." Microbiology 150, no. 5 (May 1, 2004): 1215–24. http://dx.doi.org/10.1099/mic.0.26889-0.
Full textAbstract:
The uptake, biosynthesis and catabolism of polyamines in the microsporidian parasite Encephalitozoon cuniculi are detailed with reference to the effects of oligoamine and arylamine analogues of polyamines. Enc. cuniculi, an intracellular parasite of mammalian cells, has both biosynthetic and catabolic enzymes of polyamine metabolism, as demonstrated in cell-free extracts of mature spores. The uptake of polyamines was measured in immature, pre-emergent spores isolated from host cells by Percoll gradient. Spermine was rapidly taken up and metabolized to spermidine and an unknown, possibly acetamidopropanal, by spermidine/spermine N 1-acetyltransferase (SSAT) and polyamine oxidase (PAO). Most of the spermidine and the unknown product were found in the cell incubation medium, indicating they were released from the cell. bis(Ethyl) oligoamine analogues of polyamines, such as SL-11144 and SL-11158, as well as arylamine analogues [BW-1, a bis(phenylbenzyl) 3-7-3 analogue] blocked uptake and interconversion of spermine at micromolar levels and, in the case of BW-1, acted as substrate for PAO. The Enc. cuniculi PAO activity differed from that found in mammalian cells with respect to pH optimum, substrate specificity and sensitivity to known PAO inhibitors. SL-11158 inhibited SSAT activity with a mixed type of inhibition in which the analogue had a 70-fold higher affinity for the enzyme than the natural substrate, spermine. The interest in Enc. cuniculi polyamine metabolism and the biochemical effects of these polyamine analogues is warranted since they cure model infections of Enc. cuniculi in mice and are potential candidates for human clinical trials.
39
Sakamoto, Akihiko, Junpei Sahara, Gota Kawai, Kaneyoshi Yamamoto, Akira Ishihama, Takeshi Uemura, Kazuei Igarashi, Keiko Kashiwagi, and Yusuke Terui. "Cytotoxic Mechanism of Excess Polyamines Functions through Translational Repression of Specific Proteins Encoded by Polyamine Modulon." International Journal of Molecular Sciences 21, no. 7 (March 31, 2020): 2406. http://dx.doi.org/10.3390/ijms21072406.
Full textAbstract:
Excessive accumulation of polyamines causes cytotoxicity, including inhibition of cell growth and a decrease in viability. We investigated the mechanism of cytotoxicity caused by spermidine accumulation under various conditions using an Escherichia coli strain deficient in spermidine acetyltransferase (SAT), a key catabolic enzyme in controlling polyamine levels. Due to the excessive accumulation of polyamines by the addition of exogenous spermidine to the growth medium, cell growth and viability were markedly decreased through translational repression of specific proteins [RMF (ribosome modulation factor) and Fis (rRNA transcription factor) etc.] encoded by members of polyamine modulon, which are essential for cell growth and viability. In particular, synthesis of proteins that have unusual locations of the Shine–Dalgarno (SD) sequence in their mRNAs was inhibited. In order to elucidate the molecular mechanism of cytotoxicity by the excessive accumulation of spermidine, the spermidine-dependent structural change of the bulged-out region in the mRNA at the initiation site of the rmf mRNA was examined using NMR analysis. It was suggested that the structure of the mRNA bulged-out region is affected by excess spermidine, so the SD sequence of the rmf mRNA cannot approach initiation codon AUG.
40
SUPPOLA, Suvikki, Sami HEIKKINEN, Jyrki J. PARKKINEN, Mikko UUSI-OUKARI, Veli-Pekka KORHONEN, Tuomo KEINÄNEN, Leena ALHONEN, and Juhani JÄNNE. "Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice." Biochemical Journal 358, no. 2 (August 24, 2001): 343–48. http://dx.doi.org/10.1042/bj3580343.
Full textAbstract:
We have generated a hybrid transgenic mouse line overexpressing both ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) under the control of the mouse metallothionein (MT) I promoter. In comparison with singly transgenic animals overexpressing SSAT, the doubly transgenic mice unexpectedly displayed much more striking signs of activated polyamine catabolism, as exemplified by a massive putrescine accumulation and an extreme reduction of hepatic spermidine and spermine pools. Interestingly, the profound depletion of the higher polyamines in the hybrid animals occurred in the presence of strikingly high ODC activity and tremendous putrescine accumulation. Polyamine catabolism in the doubly transgenic mice could be enhanced further by administration of zinc or the polyamine analogue N1,N11-diethylnorspermine. In tracer experiments with [14C]spermidine we found that, in comparison with syngenic animals, both MT-ODC and MT-SSAT mice possessed an enhanced efflux mechanism for hepatic spermidine. In the MT-ODC animals this mechanism apparently operated in the absence of measurable SSAT activity. In the hybrid animals, spermidine efflux was stimulated further in comparison with the singly transgenic animals. In spite of a dramatic accumulation of putrescine and a profound reduction of the spermidine and spermine pools, only marginal changes were seen in the level of ODC antizyme. Even though the hybrid animals showed no liver or other organ-specific overt toxicity, except an early and permanent loss of hair, their life span was greatly reduced. These results can be understood from the perspective that catabolism is the overriding regulatory mechanism in the metabolism of the polyamines and that, even under conditions of severe depletion of spermidine and spermine, extremely high tissue pools of putrescine are not driven further to replenish the pools of the higher polyamines.
41
Maruta, K., R. Teradaira, N. Watanabe, T. Nagatsu, M. Asano, K. Yamamoto, T. Matsumoto, Y. Shionoya, and K. Fujita. "Simple, sensitive assay of polyamines by high-performance liquid chromatography with electrochemical detection after post-column reaction with immobilized polyamine oxidase." Clinical Chemistry 35, no. 8 (August 1, 1989): 1694–96. http://dx.doi.org/10.1093/clinchem/35.8.1694.
Full textAbstract:
Abstract This simple, rapid liquid-chromatographic assay of urinary polyamines (putrescine, spermidine, spermine, and cadaverine) involves electrochemical detection with a post-column immobilized enzyme, polyamine oxidase (EC 1.4.3.6) from soybean seedlings. Polyamines are separated by isocratic ion-pairing reversed-phase chromatography, then enzymatically converted, with release of hydrogen peroxide, via the post-column reactor with immobilized polyamine oxidase; the hydrogen peroxide is detected by electrochemical oxidation on a platinum electrode. The detection limits for injected putrescine, spermidine, and spermine were 0.3, 0.5, 0.6, and 4 pmol, respectively, with linear ranges of two to three orders of magnitude. Reproducibility was also good, with CV values less than 7%. The efficiency of the immobilized enzyme column was not decreased after analysis of 300 urine samples. Putrescine and spermidine excretion in urine from patients with blood cancers and solid cancers was significantly increased.
42
Broquedis, Michel, B. Dumery, and Jacques Bouard. "Mise en évidence de polyamines (putrescine, cadaverine, nor-spermidine, spermidine et spermine) dans les feuilles et les grappes de Vitis vinifera L." OENO One 23, no. 1 (March 31, 1989): 1. http://dx.doi.org/10.20870/oeno-one.1989.23.1.1726.
Full textAbstract:
<p style="text-align: justify;">Cinq polyamines libres, la putrescine, la cadavérine, la nor-spermidine, la spermidine et la spermine, ont été mises en évidence dans les feuilles et les grappes du Cabernet- Sauvignon et de l'Ugni blanc. La spermidine est toujours la polyamine la plus abondante. La cadavérine est faiblement représentée ou absente selon le cépage ou l'organe considéré.</p>
43
Mein, Hannah, Yu Jing, Faraz Ahmad, Hu Zhang, and Ping Liu. "Altered Brain Arginine Metabolism and Polyamine System in a P301S Tauopathy Mouse Model: A Time-Course Study." International Journal of Molecular Sciences 23, no. 11 (May 27, 2022): 6039. http://dx.doi.org/10.3390/ijms23116039.
Full textAbstract:
Altered arginine metabolism (including the polyamine system) has recently been implicated in the pathogenesis of tauopathies, characterised by hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) accumulation in the brain. The present study, for the first time, systematically determined the time-course of arginine metabolism changes in the MAPT P301S (PS19) mouse brain at 2, 4, 6, 8 and 12 months of age. The polyamines putrescine, spermidine and spermine are critically involved in microtubule assembly and stabilization. This study, therefore, further investigated how polyamine biosynthetic and catabolic enzymes changed in PS19 mice. There were general age-dependent increases of L-arginine, L-ornithine, putrescine and spermidine in the PS19 brain (particularly in the hippocampus and parahippocampal region). While this profile change clearly indicates a shift of arginine metabolism to favor polyamine production (a polyamine stress response), spermine levels were decreased or unchanged due to the upregulation of polyamine retro-conversion pathways. Our results further implicate altered arginine metabolism (particularly the polyamine system) in the pathogenesis of tauopathies. Given the role of the polyamines in microtubule assembly and stabilization, future research is required to understand the functional significance of the polyamine stress response and explore the preventive and/or therapeutic opportunities for tauopathies by targeting the polyamine system.
44
Davis, R. H., P. Lieu, and J. L. Ristow. "Neurospora mutants affecting polyamine-dependent processes and basic amino acid transport mutants resistant to the polyamine inhibitor, alpha-difluoromethylornithine." Genetics 138, no. 3 (November 1, 1994): 649–55. http://dx.doi.org/10.1093/genetics/138.3.649.
Full textAbstract:
Abstract Polyamines (spermidine and spermine) are required by living cells, but their functions are poorly understood. Mutants of Neurospora crassa with enhanced or diminished sensitivity to interference with polyamine synthesis, originally selected to study the regulation of the pathway, were found to have unexpected defects. A group of four non-allelic mutations, causing no interference with polyamine synthesis, each imparted spermidine auxotrophy to a genotype already partially impaired in spermidine synthesis. Strains carrying only the new mutations displayed unconditional delay or weakness at the onset of growth, but grew well thereafter and had a normal or overly active polyamine pathway. These mutants may have defects in vital macromolecular activities that are especially dependent upon the polyamines-activities that have not been identified with certainty in studies to date. Another group of mutants, selected as resistant to the polyamine inhibitor difluoromethylornithine (DFMO), had normal activity and regulation of ornithine decarboxylase, the target of the drug. All but one of thirty mutants were allelic, and were specifically deficient in the basic amino acid permease. This mechanism of DFMO resistance is unprecedented among the many DFMO-resistant cell types of other organisms and demonstrates that DFMO can be used for efficient genetic studies of this transport locus in N. crassa.
45
Lu, Chung-Dar, Yoshifumi Itoh, Yuji Nakada, and Ying Jiang. "Functional Analysis and Regulation of the Divergent spuABCDEFGH-spuI Operons for Polyamine Uptake and Utilization in Pseudomonas aeruginosa PAO1." Journal of Bacteriology 184, no. 14 (July 15, 2002): 3765–73. http://dx.doi.org/10.1128/jb.184.14.3765-3773.2002.
Full textAbstract:
ABSTRACT A multiple-gene locus for polyamine uptake and utilization was discovered in Pseudomonas aeruginosa PAO1. This locus contained nine genes designated spuABCDEFGHI (spu for spermidine and putrescine utilization). The physiological functions of the spu genes in utilization of two polyamines (putrescine and spermidine) were analyzed by using Tn5 transposon-mediated spu knockout mutants. Growth and uptake experiments support that the spuDEFGH genes specify components of a major ABC-type transport system for spermidine uptake, and enzymatic measurements indicated that spuC encodes putrescine aminotransferase with pyruvate as the amino group receptor. Although spuA and spuB mutants showed an apparent defect in spermidine utilization, the biochemical functions of the gene products have yet to be elucidated. Assays of lacZ fusions demonstrated the presence of agmatine-, putrescine-, and spermidine-inducible promoters for the spuABCDEFGH operon and the divergently transcribed spuI gene of unknown function. Since the observed induction effect of agmatine was abolished in an aguA mutant where conversion of agmatine into putrescine was blocked, putrescine or spermidine, but not agmatine, serves as the inducer molecule of the spuA-spuI divergent promoters. S1 nuclease mappings confirmed further the induction effects of the polyamines on transcription of the divergent promoters and localized the transcription initiation sites. Gel retardation assays with extracts from the cells grown on putrescine or spermidine demonstrated the presence of a polyamine-responsive regulatory protein interacting with the divergent promoter region. Finally, the absence of the putrescine-inducible spuA expression and putrescine aminotransferase (spuC) formation in the cbrB mutant indicated that the spu operons are regulated by the global CbrAB two-component system perhaps via the putative polyamine-responsive transcriptional activator.
46
Hyvönen, Mervi T., Maxim Khomutov, Jouko Vepsäläinen, Alex R. Khomutov, and Tuomo A. Keinänen. "α-Difluoromethylornithine-Induced Cytostasis is Reversed by Exogenous Polyamines, Not by Thymidine Supplementation." Biomolecules 11, no. 5 (May 10, 2021): 707. http://dx.doi.org/10.3390/biom11050707.
Full textAbstract:
Polyamine spermidine is essential for the proliferation of eukaryotic cells. Administration of polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO) induces cytostasis that occurs in two phases; the early phase which can be reversed by spermidine, spermine, and some of their analogs, and the late phase which is characterized by practically complete depletion of cellular spermidine pool. The growth of cells at the late phase can be reversed by spermidine and by very few of its analogs, including (S)-1-methylspermidine. It was reported previously (Witherspoon et al. Cancer Discovery 3(9); 1072–81, 2013) that DFMO treatment leads to depletion of cellular thymidine pools, and that exogenous thymidine supplementation partially prevents DFMO-induced cytostasis without affecting intracellular polyamine pools in HT-29, SW480, and LoVo colorectal cancer cells. Here we show that thymidine did not prevent DFMO-induced cytostasis in DU145, LNCaP, MCF7, CaCo2, BT4C, SV40MES13, HepG2, HEK293, NIH3T3, ARPE19 or HT-29 cell lines, whereas administration of functionally active mimetic of spermidine, (S)-1-methylspermidine, did. Thus, the effect of thymidine seems to be specific only for certain cell lines. We conclude that decreased polyamine levels and possibly also distorted pools of folate-dependent metabolites mediate the anti-proliferative actions of DFMO. However, polyamines are necessary and sufficient to overcome DFMO-induced cytostasis, while thymidine is generally not.
47
Morgan, D. M. L. "Uptake of polyamines by human endothelial cells. Characterization and lack of effect of agonists of endothelial function." Biochemical Journal 286, no. 2 (September 1, 1992): 413–17. http://dx.doi.org/10.1042/bj2860413.
Full textAbstract:
Uptake of polyamines by confluent monolayers of human umbilical-vein endothelial cells (HUVECs) was found to be time-, temperature- and concentration-dependent, energy-requiring, and saturable. Kinetic constants were putrescine Kt 3 +/- 1 microM, Vmax. 15 +/- 7 pmol/h per microgram of protein; spermidine, 0.7 +/- 0.2, 12 +/- 3; spermine, 1 +/- 0.7, 11 +/- 4. Putrescine uptake was inhibited by spermine or spermidine, whereas uptake of spermine or spermidine was not inhibited by 20 microM-putrescine. These data suggest the existence of two carriers, one shared by spermine and spermidine, and one capable of transporting all three polyamines. Pretreatment of HUVECs with thrombin (less than or equal to 10 units/ml; 1 h), bradykinin (less than or equal to 10 microM; 1 h), interleukin-1 (less than or equal to 100 units/ml; 2 h) or phorbol 12-myristate 13-acetate (less than or equal to 1.0 microM; 1 h), all known agonists of endothelial function, had no significant effect on polyamine uptake. These responses may be of importance in angiogenesis and wound healing, and could have pharmacological significance, for there is a growing interest in the use of polyamines or polyamine analogues as therapeutic agents.
48
Riaza Bermudo-Soriano, C., C. Vaquero-Lorenzo, M. Dîaz-Hernândez, M. Garda Dorado, P. Sânchez-Pâez, I. Durân Cristobal, R. Manzanero Estopinân, et al. "Blood polyamine levels in drug-free schizophrenics." European Psychiatry 26, S2 (March 2011): 1492. http://dx.doi.org/10.1016/s0924-9338(11)73196-0.
Full textAbstract:
BackgroundNatural polyamines (putrescine, spermidine and spermine) are low molecular weight highly protonated aliphatic molecules that physiologically modulate NMDA, AMPA/kainate glutamatergic receptors and limbic dopaminergic neurotransmission. Previous studies had demonstrated that polyamine metabolism might be disrupted in schizophrenia, what could potentially be linked to glutamatergic dysfunction. In particular, polyamine levels in blood and fibroblast cultures from patients with schizophrenia had previously been found to be higher than in healthy controls. Indeed, a significant positive correlation between blood polyamine levels and severity of illness may exist.MethodsIn order to test potential differences in blood polyamine levels between drug-free schizophrenia in-patients (n = 12), and healthy controls (n = 26, blood donors), spermidine (spd), spermine (spm), and spermidine/spermine index (spd/spm) were determined using HPLC after dansylation.ResultsNo significant differences were found between groups (t = 0,974; df = 36; P = 0,337 for spd, t = l0, 52; df = 36; P = 0,959 for Spm, and, t = 0, 662; df = 36; P = 0,512 for spd/spm).ConclusionsThough we couldn’t replicate previous findings suggesting disturbances in blood polyamine levels in schizophrenia, this issue may be a promising target. Future research should take into account possible factors such as sex, nutritional state, and stress.
49
LINDSAY, Gayle S., and Heather M. WALLACE. "Changes in polyamine catabolism in HL-60 human promyelogenous leukaemic cells in response to etoposide-induced apoptosis." Biochemical Journal 337, no. 1 (December 17, 1998): 83–87. http://dx.doi.org/10.1042/bj3370083.
Full textAbstract:
The topoisomerase II inhibitor etoposide induced apoptosis in HL-60 cells within 4 h of exposure to the drug, as measured by changes in morphology, DNA fragmentation and cytotoxicity assays. Etoposide-induced apoptosis was accompanied by an increase in polyamine efflux from the cells and a decrease in total polyamine content during the first 24 h of exposure to the drug. Although both enzyme activities increased slightly, there were no significant changes in spermidine/spermine N1-acetyltransferase activity or polyamine oxidase activity. After longer exposures (48–72 h), significant induction of spermidine/spermine N1-acetyltransferase activity and loss of polyamine content occurred. These results suggest that polyamine oxidation and the resultant hydrogen peroxide produced may be associated with the initiation of apoptosis, while induction of the acetyltransferase and overall loss of intracellular polyamines may be involved in the final, possibly necrotic, stages of cell death.
50
Yoldaş İlktaç, Havvanur, Nihal Büyükuslu, and Cüneyd Parlayan. "The combined supplementation of omega-3 fatty acids and probiotics decreased the levels of serum polyamines in experimental colitis." Food and Health 7, no. 4 (2021): 279–85. http://dx.doi.org/10.3153/fh21029.
Full textAbstract:
Polyamines play an important role in the maintenance of intestinal permeability. Therefore we aimed to determine the effects of probiotics and omega 3 fatty acids on serum polyamine levels in colitis. Fifty BALB/c mice were randomly grouped as normal, colitis with no treatment applied, colitis treated by probiotics (VSL#3), colitis treated by omega-3, and colitis treated by both probiotics and omega-3. Experimental colitis was induced by injection of 200 mg/kg 2,4-Dinitrobenzenesulfonic acid (DNBS). The probiotic and the omega-3 fatty acid supplements were applied daily by oral gavage. Serum polyamine levels were measured with high performance liquid chromatography (HPLC). In each group, the levels of serum polyamines are the highest in spermidine and the least in spermine. Bowel inflammation in experimentally induced colitis mice resulted in lower serum polyamine concentrations. In probiotic and omega 3 fatty acid supplemented group significant decreases were observed for spermine and spermidine (p<0.001), while no significant changes were obtained for putrescine. Combined supplementation of probiotics and omega-3 fatty acids for 10 days in colitis mice significantly decreased the serum levels of spermine and spermidine.