Academic literature on the topic 'Protein metabolsim'
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Journal articles on the topic "Protein metabolsim"
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Li, Quan, Xiangyang Li, and Hui Lin. "Proteomic Analysis Reveals Growth Inhibition of Coriolus versicolor by Methanol Extracts of Cinnamomum camphora Xylem." International Journal of Polymer Science 2021 (August 21, 2021): 1–9. http://dx.doi.org/10.1155/2021/6337906.
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The extracts of decay-resistant tree species are important research objects for the future development of wood preservatives. To understand the antifungal mechanisms of Coriolus versicolor inhibition with methanol extracts of C. camphora xylem, the protein profiles of C. versicolor were analyzed using 2-DE followed by MALDI-TOF/MS and bioinformatic analyses. The results showed that 41 protein spots were obviously changed among the 366-385 protein spots of C. versicolor treated with methanol extracts of C. camphora xylem. Twenty-one protein spots were upregulated, and 20 protein spots were downregulated. Cellular localization was performed to identify these differential proteins, and biological process and functional analysis found that 9 of these proteins were in the cytoplasm, 6 were intracellular, and 5 were in the mitochondrion. A total of 18.8% were mapped to small-molecule metabolic processes, 12.5% to cellular amino acid metabolic processes, and 10.9% to cellular nitrogen compound metabolic processes. Twenty-five percent of the differential proteins were associated with ion bonding, 15% with oxidoreductase activity, and 15% with ATPase activity and transmembrane transport activity. Downregulated expression of aspartate aminotransferase, ATP synthase alpha chain, DEAD/DEAH-box helicase, and phosphoglycerate kinase showed that the methanol extracts of C. camphora xylem disrupted functional aspects such as nitrogen and carbon metabolism, energy metabolism, hormone signal response, and glucose metabolism, eventually leading to C. versicolor inhibition.
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Slayton, Mark, Abhishek Gupta, Bijinu Balakrishnan, and Vishwajeet Puri. "CIDE Proteins in Human Health and Disease." Cells 8, no. 3 (March 13, 2019): 238. http://dx.doi.org/10.3390/cells8030238.
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Cell death-Inducing DNA Fragmentation Factor Alpha (DFFA)-like Effector (CIDE) proteins have emerged as lipid droplet-associated proteins that regulate fat metabolism. There are three members in the CIDE protein family—CIDEA, CIDEB, and CIDEC (also known as fat-specific protein 27 (FSP27)). CIDEA and FSP27 are primarily expressed in adipose tissue, while CIDEB is expressed in the liver. Originally, based upon their homology with DNA fragmentation factors, these proteins were identified as apoptotic proteins. However, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. Despite various studies in humans and gene-targeting studies in mice, the physiological roles of CIDE proteins remains elusive. This review will summarize the known physiological role and metabolic pathways regulated by the CIDE proteins in human health and disease.
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Aleshin, Vasily A., Artem V. Artiukhov, Thilo Kaehne, Anastasia V. Graf, and Victoria I. Bunik. "Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293." International Journal of Molecular Sciences 22, no. 15 (July 27, 2021): 8006. http://dx.doi.org/10.3390/ijms22158006.
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Coupling glycolysis and mitochondrial tricarboxylic acid cycle, pyruvate dehydrogenase (PDH) complex (PDHC) is highly responsive to cellular demands through multiple mechanisms, including PDH phosphorylation. PDHC also produces acetyl-CoA for protein acetylation involved in circadian regulation of metabolism. Thiamine (vitamin B1) diphosphate (ThDP) is known to activate PDH as both coenzyme and inhibitor of the PDH inactivating kinases. Molecular mechanisms integrating the function of thiamine-dependent PDHC into general redox metabolism, underlie physiological fitness of a cell or an organism. Here, we characterize the daytime- and thiamine-dependent changes in the rat brain PDHC function, expression and phosphorylation, assessing their impact on protein acetylation and metabolic regulation. Morning administration of thiamine significantly downregulates both the PDH phosphorylation at Ser293 and SIRT3 protein level, the effects not observed upon the evening administration. This action of thiamine nullifies the daytime-dependent changes in the brain PDHC activity and mitochondrial acetylation, inducing diurnal difference in the cytosolic acetylation and acetylation of total brain proteins. Screening the daytime dependence of central metabolic enzymes and proteins of thiol/disulfide metabolism reveals that thiamine also cancels daily changes in the malate dehydrogenase activity, opposite to those of the PDHC activity. Correlation analysis indicates that thiamine abrogates the strong positive correlation between the total acetylation of the brain proteins and PDHC function. Simultaneously, thiamine heightens interplay between the expression of PDHC components and total acetylation or SIRT2 protein level. These thiamine effects on the brain acetylation system change metabolic impact of acetylation. The changes are exemplified by the thiamine enhancement of the SIRT2 correlations with metabolic enzymes and proteins of thiol-disulfide metabolism. Thus, we show the daytime- and thiamine-dependent changes in the function and phosphorylation of brain PDHC, contributing to regulation of the brain acetylation system and redox metabolism. The daytime-dependent action of thiamine on PDHC and SIRT3 may be of therapeutic significance in correcting perturbed diurnal regulation.
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Olalde-Portugal, Víctor, José Luis Cabrera-Ponce, Argel Gastelum-Arellanez, Armando Guerrero-Rangel, Robert Winkler, and Silvia Valdés-Rodríguez. "Proteomic analysis and interactions network in leaves of mycorrhizal and nonmycorrhizal sorghum plants under water deficit." PeerJ 8 (April 23, 2020): e8991. http://dx.doi.org/10.7717/peerj.8991.
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For understanding the water deficit stress mechanism in sorghum, we conducted a physiological and proteomic analysis in the leaves of Sorghum bicolor L. Moench (a drought tolerant crop model) of non-colonized and colonized plants with a consortium of arbuscular mycorrhizal fungi. Physiological results indicate that mycorrhizal fungi association enhances growth and photosynthesis in plants, under normal and water deficit conditions. 2D-electrophoresis profiles revealed 51 differentially accumulated proteins in response to water deficit, of which HPLC/MS successfully identified 49. Bioinformatics analysis of protein–protein interactions revealed the participation of different metabolic pathways in nonmycorrhizal compared to mycorrhizal sorghum plants under water deficit. In noninoculated plants, the altered proteins are related to protein synthesis and folding (50S ribosomal protein L1, 30S ribosomal protein S10, Nascent polypeptide-associated complex subunit alpha), coupled with multiple signal transduction pathways, guanine nucleotide-binding beta subunit (Rack1) and peptidyl-prolyl-cis-trans isomerase (ROC4). In contrast, in mycorrhizal plants, proteins related to energy metabolism (ATP synthase-24kDa, ATP synthase β), carbon metabolism (malate dehydrogenase, triosephosphate isomerase, sucrose-phosphatase), oxidative phosphorylation (mitochondrial-processing peptidase) and sulfur metabolism (thiosulfate/3-mercaptopyruvate sulfurtransferase) were found. Our results provide a set of proteins of different metabolic pathways involved in water deficit produced by sorghum plants alone or associated with a consortium of arbuscular mycorrhizal fungi isolated from the tropical rain forest Los Tuxtlas Veracruz, México.
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Chiang, John Y. L., Preeti Pathak, Hailiang Liu, Ajay Donepudi, Jessica Ferrell, and Shannon Boehme. "Intestinal Farnesoid X Receptor and Takeda G Protein Couple Receptor 5 Signaling in Metabolic Regulation." Digestive Diseases 35, no. 3 (2017): 241–45. http://dx.doi.org/10.1159/000450981.
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Bile acids play a critical role in the regulation of glucose, lipid and energy metabolisms by activating the nuclear bile acid receptor farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (aka takeda G protein couple receptor 5, TGR5) signaling. Paradoxical roles of FXR in the regulation of glucose and lipid metabolism and metabolic disorder have been reported recently. The activation or inhibition of intestinal FXR signaling has been shown to improve insulin and glucose sensitivity and energy metabolism to prevent diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). TGR5 has an anti-inflammatory function in the intestine and stimulates glucagon-like peptide-1 (GLP-1) secretion in the intestine to stimulate insulin secretion from the pancreas. The role of TGR5 in metabolism and metabolic regulation is not clear and warrants further study. FXR and TGR5 are co-expressed in the ileum and colon. These 2 bile acid-activated receptors may cooperate to stimulate GLP-1 secretion and improve hepatic metabolism. FXR and TGR5 dual agonists may have therapeutic potential for treating diabetes and NAFLD.
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Phillips, Darci, Angel M. Aponte, Raul Covian, Edward Neufeld, Zu-Xi Yu, and Robert S. Balaban. "Homogenous protein programming in the mammalian left and right ventricle free walls." Physiological Genomics 43, no. 21 (November 2011): 1198–206. http://dx.doi.org/10.1152/physiolgenomics.00121.2011.
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Despite identical cardiac outputs, the right (RV) and left ventricle (LV) have very different embryological origins and resting workload. These differences suggest that the ventricles have different protein programming with regard to energy metabolism and contractile elements. The objective of this study was to determine the relative RV and LV protein expression levels, with an emphasis on energy metabolism. The RV and LV protein contents of the rabbit and porcine heart were determined with quantitative gel electrophoresis (2D-DIGE), mass spectrometry, and optical spectroscopy techniques. Surprisingly, the expression levels for more than 600 RV and LV proteins detected were similar. This included proteins many different compartments and metabolic pathways. In addition, no isoelectric shifts were detected in 2D-DIGE consistent with no differential posttranslational modifications in these proteins. Analysis of the RV and LV metabolic response to work revealed that the metabolic rate increases much faster with workload in the RV compared with LV. This implies that the generally lower metabolic stress of the RV actually approaches LV metabolic stress at maximum workloads. Thus, identical levels of energy conversion and mechanical elements in the RV and LV may be driven by the performance requirements at maximum workloads. In summary, the ventricles of the heart manage the differences in overall workload by modifying the amounts of cytosol, not its composition. The constant myocyte composition in the LV and RV implies that the ratio of energy metabolism and contractile elements may be optimal for the sustained cardiac contractile activity in the mammalian heart.
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Zhou, Suping, Marsha Palmer, Jing Zhou, Sarabjit Bhatti, Kevin J. Howe, Tara Fish, and Theodore W. Thannhauser. "Differential Root Proteome Expression in Tomato Genotypes with Contrasting Drought Tolerance Exposed to Dehydration." Journal of the American Society for Horticultural Science 138, no. 2 (March 2013): 131–41. http://dx.doi.org/10.21273/jashs.138.2.131.
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A comparative proteomics study using isobaric tags for relative and absolute quantitation (iTRAQ) was performed on a mesophytic tomato (Solanum lycopersicum) cultivar and a dehydration-resistant wild species (Solanum chilense) to identify proteins that play key roles in tolerance to water deficit stress. In tomato ‘Walter’ LA3465, 130 proteins were identified, of which 104 (80%) were repressed and 26 (20%) were induced. In S. chilense LA1958, a total of 170 proteins were identified with 106 (62%) repressed and 64 (38%) induced. According to their putative molecular functions, the differentially expressed proteins belong to the following subgroups: stress proteins, gene expression, nascent protein processing, protein folding, protein degradation, carbohydrate metabolism, amino acid and nucleotide metabolism, lipid metabolism, signal transduction, and cell cycle regulation. Based on changes in protein abundance induced by the dehydration treatment, cellular metabolic activities and protein biosynthesis were suppressed by the stress. In S. chilense, dehydration treatment led to elevated accumulation of proteins involved in post-transcriptional gene regulation and fidelity in protein translation including prefoldin, which promotes protein folding without the use of adenosine-5′-triphosphate (ATP), several hydrophilic proteins, and calmodulin in the calcium signal transduction pathway. Those protein changes were not found in the susceptible tomato, ‘Walter’. Within each functional protein group, proteins showing opposite changes (dehydration induced vs. repressed) in the two species were identified and roles of those proteins in conferring tolerance to water deficit stress are discussed. Information provided in this report will be useful for selection of proteins or genes in analyzing or improving dehydration tolerance in tomato cultivars.
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Herrmann, Abigail G., Ruth F. Deighton, Thierry Le Bihan, Mailis C. McCulloch, James L. Searcy, Lorraine E. Kerr, and James McCulloch. "Adaptive Changes in the Neuronal Proteome: Mitochondrial Energy Production, Endoplasmic Reticulum Stress, and Ribosomal Dysfunction in the Cellular Response to Metabolic Stress." Journal of Cerebral Blood Flow & Metabolism 33, no. 5 (January 16, 2013): 673–83. http://dx.doi.org/10.1038/jcbfm.2012.204.
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Impaired energy metabolism in neurons is integral to a range of neurodegenerative diseases, from Alzheimer's disease to stroke. To investigate the complex molecular changes underpinning cellular adaptation to metabolic stress, we have defined the proteomic response of the SH-SY5Y human neuroblastoma cell line after exposure to a metabolic challenge of oxygen glucose deprivation (OGD) in vitro. A total of 958 proteins across multiple subcellular compartments were detected and quantified by label-free liquid chromatography mass spectrometry. The levels of 130 proteins were significantly increased ( P < 0.01) after OGD and the levels of 63 proteins were significantly decreased ( P < 0.01) while expression of the majority of proteins (765) was not altered. Network analysis identified novel protein–protein interactomes involved with mitochondrial energy production, protein folding, and protein degradation, indicative of coherent and integrated proteomic responses to the metabolic challenge. Approximately one third (61) of the differentially expressed proteins was associated with the endoplasmic reticulum and mitochondria. Electron microscopic analysis of these subcellular structures showed morphologic changes consistent with the identified proteomic alterations. Our investigation of the global cellular response to a metabolic challenge clearly shows the considerable adaptive capacity of the proteome to a slowly evolving metabolic challenge.
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Zhao, Zifeng, Lei Yin, Feihua Wu, and Xin Tong. "Hepatic metabolic regulation by nuclear factor E4BP4." Journal of Molecular Endocrinology 66, no. 1 (January 2021): R15—R21. http://dx.doi.org/10.1530/jme-20-0239.
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Discovered as a b-ZIP transcription repressor 30 years ago, E4 promoter-binding protein 4 (E4BP4) has been shown to play critical roles in immunity, circadian rhythms, and cancer progression. Recent research has highlighted E4BP4 as a novel regulator of metabolisms in various tissues. In this review, we focus on the function and mechanisms of hepatic E4BP4 in regulating lipid and glucose homeostasis, bile metabolism, as well as xenobiotic metabolism. Finally, E4BP4-specific targets will be discussed for the prevention and treatment of metabolic disorders.
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Xu, Man, Run-Qing Xue, Yi Lu, Su-Yun Yong, Qing Wu, Yan-Ling Cui, Xiao-Ting Zuo, Xiao-Jiang Yu, Ming Zhao, and Wei-Jin Zang. "Choline ameliorates cardiac hypertrophy by regulating metabolic remodelling and UPRmt through SIRT3-AMPK pathway." Cardiovascular Research 115, no. 3 (August 27, 2018): 530–45. http://dx.doi.org/10.1093/cvr/cvy217.
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Abstract Aims Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline. Methods and results The experiments were conducted using a model of ventricular hypertrophy by partially banding the abdominal aorta of Sprague Dawley rats. Cardiomyocyte size and cardiac fibrosis were significantly increased in hypertrophic hearts. In vitro cardiomyocyte hypertrophy was induced by exposing neonatal rat cardiomyocytes to angiotensin II (Ang II) (10−6 M, 24 h). Choline attenuated the mito-nuclear protein imbalance and activated the mitochondrial-unfolded protein response (UPRmt) in the heart, thereby preserving the ultrastructure and function of mitochondria in the context of cardiac hypertrophy. Moreover, choline inhibited myocardial metabolic dysfunction by promoting the expression of proteins involved in ketone body and fatty acid metabolism in response to pressure overload, accompanied by the activation of sirtuin 3/AMP-activated protein kinase (SIRT3-AMPK) signalling. In vitro analyses demonstrated that SIRT3 siRNA diminished choline-mediated activation of ketone body metabolism and UPRmt, as well as inhibition of hypertrophic signals. Intriguingly, serum from choline-treated abdominal aorta banding models (where β-hydroxybutyrate was increased) attenuated Ang II-induced myocyte hypertrophy, which indicates that β-hydroxybutyrate is important for the cardioprotective effects of choline. Conclusion Choline attenuated cardiac dysfunction by modulating the expression of proteins involved in ketone body and fatty acid metabolism, and induction of UPRmt; this was likely mediated by activation of the SIRT3-AMPK pathway. Taken together, these results identify SIRT3-AMPK as a key cardiac transcriptional regulator that helps orchestrate an adaptive metabolic response to cardiac stress. Choline treatment may represent a new therapeutic strategy for optimizing myocardial metabolism in the context of hypertrophy and heart failure.
Dissertations / Theses on the topic "Protein metabolsim"
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Pacy, P. J. H. "Influence of insulin and glucagon on protein metabolism and resting metabolic rate." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234726.
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Reaich, David. "Protein and carbohydrate metabolism in metabolic acidosis." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308003.
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Chronic renal failure (CRF) is associated with loss of lean body mass, a high incidence of malnutrition, and with insulin resistance. CRF is often complicated by metabolic acidosis. Metabolic acidosis is known to alter both protein and carbohydrate metabolism. A series of studies have been undertaken to investigate the effect of metabolic acidosis on protein metabolism in both normal and CRF human subjects, and to study whether metabolic acidosis in CRF affects insulin sensitivity. Protein turnover was studied using the technique of primed constant infusions of L-[1-13C]leucine. Normal subjects were studied before and after ammonium chloride induced metabolic acidosis. Acidosis was associated with increased protein turnover and amino acid oxidation. In CRF subjects, correction of acidosis with sodium bicarbonate decreased protein turnover and amino acid oxidation. The effect of acidosis in CRF on insulin mediated carbohydrate metabolism was studied using the technique of the hyperinsulinaemic euglycaemic clamp. Insulin sensitivity increased with correction of acidosis. By combining L-[1-13C]leucine infusions with hyperinsulinaemic euglycaemic clamps, the response of protein metabolism to hyperinsulinaemia was measured before and after correction of acidosis. The presence of acidosis did not impair the ability of insulin to modulate protein metabolism. There is therefore, dissociation between the effects of acidosis in CRF on insulin mediated carbohydrate metabolism and insulin mediated protein metabolism. In summary, metabolic acidosis increases protein catabolism in both normal and CRF man and may contribute to the loss of lean body mass characteristic of CRF. Insulin resistance in CRF improves with correction of acidosis. However the effects of acidosis on protein metabolism are not mediated via alterations in insulin sensitivity.
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Cruz, Bread Leandro Gomes da 1979. "Ação in vivo de l-leucina sobre sinalização celular e vias metabólicas durante o metabolismo protéico muscular em ratos portadores de tumos Walker 256 = L-leucine-rich diet modulates muscle cell signalling pathway of protein metabolism in Walker 256 tumour-bearing rats." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314496.
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Orientador: Maria Cristina Cintra Gomes MarcondesTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O câncer é uma das principais causas de morte no mundo e o quadro de caquexia provocado por alguns tipos de tumor é um dos grandes responsáveis por isso. A caquexia instaurada em pacientes com câncer, sendo mais prevalente nos tumores gastrointestinal, pulmonar, pancreático e mamário, é caracterizada, dentre outros processos, pela perda involuntária de peso, devido a constante espoliação sobre a massa magra corporal. Estudos que tenham como objetivo a manutenção da massa magra em organismos portadores de tumor caquético são importantes para contribuir com a redução de óbitos e preservar a qualidade de vida das pessoas com câncer. Nos últimos anos, a leucina tem mostrado ser eficaz na manutenção da massa magra corpórea através do estímulo de síntese protéica muscular e inibição da degradação de proteína, principalmente da massa magra corpórea. Logo, entender como a presença da leucina estimula a síntese protéica e atua de forma protetora em organismo no estado caquético tem se mostrado uma necessidade crescente. Desse modo, a proposta deste trabalho foi avaliar, ao longo do tempo, os efeitos de dieta rica em leucina sobre a sinalização de síntese e degradação protéica, envolvendo o complexo mTOR em músculos de ratos portadores do carcinossarcoma de Walker 256. Os animais foram distribuídos em grupos de acordo com a inoculação tumoral e/ou esquema nutricional com dieta rica em leucina, sendo sacrificados em três momentos diferentes do desenvolvimento tumoral (7º, 14º e 21º dias após a implantação do tumor). No músculo gastrocnêmio foram analisadas as proteínas-chave da via mTOR, como RAG A GTPase, ERK/MAP4K3, PKB/Akt, mTOR, p70S6K1, Jnk, IRS-1, STAT3, e STAT6 e, tambem, foram avaliadas as proteínas de degradação protéica pertencentes ao sistema ubiquitina-proteossomo (11S, 19S e 20S) e citocinas IL-4, IL-6, IL-10, TNF? e INF?. Os resultados mostram que o desenvolvimento tumoral reduziu a ativação de RAG-A, associada com queda de IRS-1, aumento da PKB/Akt e Erk/MAP4K3 no 21º dia e manutenção de p70S6K1; também houve aumento dos níveis de STAT-3 e STAT-6 em ratos portadores de tumor. Entretanto, a presença de leucina na dieta modulou etapas chave da via mTOR pelo desencadeamento da ativação aumentada de RAG-A e mTOR junto com a manutenção dos níveis de JNK, STAT-3 e STAT-6 no músculo durante o desenvolvimento do tumor de Walker no organismo caquético. A análise da sinalização para degradação protéica mostrou que o crescimento tumoral promoveu, simultaneamente, diminuição de proteína muscular, acentuado aumento de citocinas pró-inflamatórias (TNF?, IL-6 e IFN?) e aumento progressivo das subunidades proteossômicas (19S e 20S), sendo que a suplementação com leucina atenuou essa ativação. Os resultados obtidos apoiam o efeito benéfico do uso de leucina e esclarece as vias metabólicas utilizadas por este aminoácido, contribuindo para melhor compreensão da ação in vivo desse aminoácido sobre a caquexia
Abstract: Cancer is one of the most important causes of death worldwide and the process of cachexia caused by some types of tumour is largely responsible for this. Cancer-cachexia state established in these patients is characterized, among other processes, by involuntary loss of weight due to constant spoliation of lean body mass. Many studies aim to focus in maintenance of lean body mass in cachectic tumour-bearing host, contributing to the reduction of deaths and improving the quality of life of cancer patients. In recent years, leucine has been shown to be effective in maintaining lean body mass by stimulating muscle protein synthesis and inhibiting the proteolysis. Therefore, there are increased needs in understanding how the presence of leucine stimulates protein synthesis and acts protectively in the cachectic state. The aim of this work is to evaluate the effects of leucine-rich diet in a time-course model on signalling protein synthesis and degradation involving mTOR complex in muscles of Walker 256 carcinoma-bearing rats. Animals were divided into experimental groups based on the tumour inoculation and/or fed a nutritional supplementation diet rich in leucine. Animals were sacrificed at three different times depending on the tumour development (7, 14 and 21 days after tumour implantation), and the gastrocnemius muscles were analysed as mTOR pathway and ubiquitin-proteasome via. The results showed that the tumour development has reduced the activation of RAG-A, associated with a decrease of IRS-1, increased PKB / Akt and Erk / MAP4K3 at day 21 and maintaining p70S6K1, there has also been increasing levels of STAT-3 and STAT-6 in tumour-bearing rats. Meanwhile, the presence of leucine in the diet modulated the key steps of the mTOR pathway for triggering the increased RAG-A and mTOR activation along with the maintenance of levels of JNK, STAT-3 and STAT-6 in the muscle during tumour development in cachectic host. The gastrocnemius muscle signalling of protein degradation indicated by the ubiquitin-proteasome subunits (11S, 19S and 20S) and pro- and anti-inflammatory cytokines were marked increase of pro-inflammatory cytokines (TNF?, IL-6 and IFN?) and a progressive increase in the proteasome subunits (19S and 20S) associated with simultaneously decreased muscle protein. The supplementation with leucine attenuated these parameters, suggesting the beneficial effect of the use of leucine and clarifies the metabolic pathways used by this amino acid, contributing to better understanding of the in vivo action of this amino acid on cachexia
Doutorado
Fisiologia
Doutor em Biologia Funcional e Molecular
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Smits, Callum, and n/a. "Structures of the pro-survival protein A1 in complex with BH3-domain peptides." University of Otago. Department of Biochemistry, 2007. http://adt.otago.ac.nz./public/adt-NZDU20071218.131743.
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Protein:protein interactions are central to the regulation of the intrinsic programmed cell death (apoptosis) pathway. Opposing members of the Bcl-2 family of proteins, which have distinct sequence features, interact with each other on the outer mitochondrial membrane to regulate apoptosis. Pro-survival proteins such as Bcl-2, Bcl-x[L], Bcl-w, Mcl-1 and A1 protect cells from apoptosis and contain up to four regions of homology to Bcl-2 (Bcl-2 homology domains 1 - 4, BH1-4). Pro-apoptotic BH3-only proteins such as Bim, Puma, Noxa, Bad, Bmf, and Bid promote apoptosis by interacting with and inactivating pro-survival proteins, and contain just the BH3-domain. The pro-apoptotic proteins Bax and Bak are essential for apoptosis and contain three regions of homology to Bcl-2 (the BH1-, BH2- and BH3-domains).
In this study, two different sets of interactions involving pro-survival proteins were investigated. Initially, the pro-apoptotic protein Bnip3 was examined to determine if it was a mitochondrial anchor for the pro-survival protein Bcl-w. Secondly, to characterise the interactions between a pro-survival protein and different BH3-domains, structures were solved of the pro-survival protein A1 in complex with four different BH3-domains.
In the structure of Bcl-w, the hydrophobic C-terminus is bound to its own BH3-domain binding groove. This location of the C-terminus is consistent with the observation that Bcl-w is only loosely associated with the outer mitochondrial membrane in healthy cells. Upon interaction of Bcl-w with a BH3-domain, Bcl-w becomes tightly associated with the mitochondrial membrane, presumably due to displacement of the C-terminal residues by the BH3-only protein. In healthy cells it has been suggested that Bcl-w is associated with the membrane due to an interaction with an unidentified membrane protein, which preliminary experiments suggested may be Bnip3. Protein interaction experiments performed in vitro and in vivo did not reveal an interaction between Bnip3 and Bcl-w.
It was originally thought that each pro-apoptotic BH3-only protein could interact with all pro-survival proteins. However, it has recently become clear that there is selectivity within the pathway suggesting functional groupings. Bim and Puma behave as originally predicted and can interact with all pro-survival proteins and are potent killers. In contrast, Noxa and Bad interact with distinct subsets of pro-survival proteins. Noxa only binds Mcl-1 and A1, while Bad binds Bcl-2, Bcl-x[L] and Bcl-w. As a result, either Noxa or Bad acting alone is a weak killer, but together they are potent. Other BH3-only proteins bind tightly to some pro-survival proteins and weakly to others.
The diversity that exists between BH3-domain sequences precludes sequence-based identification of the determinants of specificity. In this study, crystal structures of A1:Puma BH3-domain, A1:Bmf BH3-domain, A1:Bak BH3-domain and A1:Bid BH3-domain complexes have been solved. Differences identified between these structures explain some of the variation in affinities observed in pro-survival protein:BH3-domain complexes. These observations, in combination with published data, suggest that BH3-domains bind weakly when the optimal interactions with conserved residues cannot be formed. Additionally, differences were observed in the A1:Bak BH3-domain structure that may be functionally important for the regulation of Bak.
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Löfberg, Erland. "The effects of haemodialysis and metabolic acidosis on protein metabolism /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4213-7/.
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Zaffani, Viviane Costa Silva. "Avaliação do metabolismo proteico muscular de ratos alimentados com proteinas do soro do leite e submetidos a atividade fisica." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/254470.
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Orientador: Jaime Amaya-FarfanDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: A ocorrência de desvios no metabolismo protéico durante o exercício depende tanto da intensidade, duração e freqüência do exercício, como também da ingestão alimentar, especialmente da qualidade da dieta consumida. Neste contexto, proteína do soro do leite (PSL) destaca-se pelo seu alto valor nutritivo, devido tanto à composição de aminoácidos, quanto à rápida digestão, além de outras funcionalidades relacionadas com a saúde. O objetivo deste estudo foi avaliar em ratos os efeitos da ingestão da proteína do soro do leite, na sua forma intacta e hidrolisada (~12,5% de hidrólise), em associação à atividade física de endurance, sobre os níveis séricos de aminoácidos, evolução ponderal, conteúdo protéico em gastrocnêmio e sóleo, conteúdo de DNA no gastrocnêmio, níveis séricos de IGF1, síntese e degradação protéica no grastrocnêmio e síntese no sóleo. Ratos Wistar foram distribuídos em 6 grupos, de acordo com a proteína consumida (12%): caseína (CAS), isolado protéico do soro do leite (IPSL) ou hidrolisado protéico do soro do leite (HPSL)) e submetidos a um protocolo de atividade física (sedentários (S) e treinados (T)). Os ratos treinados correram em esteira, durante 9 semanas, e foram sacrificados após 48 horas de repouso e 12 horas de jejum. As três dietas utilizadas apresentaram conteúdos semelhantes de aminoácidos totais, mas as dietas IPSL e HPSL destacaram-se apresentando maiores valores absolutos de leucina, isoleucina, lisina, treonina, cistina, alanina e ácido aspártico, em relação a CAS. No geral, os níveis séricos de aminoácidos indispensáveis foram semelhantes para os grupos IS e HS, em comparação com os ratos controle sedentários (CS), enquanto o grupo HT apresentou o maior nível destes aminoácidos, em relação ao CT. A evolução ponderal foi semelhante para todos os grupos de ratos até o final da oitava semana de treinamento. Na nona semana, os grupos treinados apresentaram peso significativamente menor que o CS. Não houve diferença estatística para o peso, conteúdo protéico dos músculos gastrocnêmio e sóleo, níveis séricos de IGF1 e taxas de degradação protéica muscular do gastrocnêmio, entre todos os grupos experimentais. O conteúdo e concentração de DNA no gastrocnêmio foi significativamente menor em ambos os grupos que consumiam a HPSL (HS e HT), independente da atividade física, comparado aos grupos que consumiam as proteínas intactas (CS, IS, CT e IT). As taxas de síntese protéica nos músculos gastrocnêmio e sóleo também foram menores para o grupo HT, comparado aos sedentários (CS, IS e HS), mas sem mostrar diferença com os grupos CT e IT. Os ratos do grupo HT destacaram-se por apresentar diminuição da demanda por nova síntese protéica, e da necessidade de utilização de aminoácidos do pool sérico diminuindo, consequentemente, a necessidade de aumentar a quantidade de DNA celular no músculo gastrocnêmio e ainda assim, manteve o peso, a concentração e o conteúdo protéico muscular sem diferença em relação aos demais grupos. Estes resultados, considerados em conjunto, sugerem que o consumo da proteína hidrolisada do soro do leite pode contribuir para a preservação da massa muscular no gastrocnêmio, quando associado à atividade física de endurance.
Abstract: Physical exercise promotes protein metabolic alterations depending not only on its intensity, duration and frequency, but also on food intake and especially on the quality of the diet. In this context, the milk whey proteins (PSL) stand out because of their high quality, meeting both amino-acid profile and digestibility requirements, besides other functional properties. The aim of this study was to assess the effects of milk whey protein intake in rats, in both the intact and hydrolyzed forms (~12,5% of hydrolysis), associated with physical activity of endurance, on serum amino acids levels, body weight, protein content in both the gastrocnemius and soleus muscles, total DNA content in the gastrocnemius, serum IGF1 levels, protein degradation rate in the gastrocnemius, and of protein synthesis in the soleus and gastrocnemius. Male Wistar rats were divided into six groups as follows: protein consumed (12%), casein - CAS, milk whey protein isolate - IPSL, or milk whey protein hydrolyzate -HPSL) and physical activity protocol (sedentary, S, and trained, T). The trained rats were exercised on the treadmill during nine weeks and sacrificed following 48 hours of rest; the last 12 hours being fasted. The three diets tested produced similar contents of total amino acids, although the IPSL and HPSL diets stood out because of the higher absolute values of leucine, isoleucine, lysine, threonine, cysteine, alanine and aspartate than those of CAS. As a whole, the serum indispensable amino acid levels were similar when comparing both IS and HS groups with the control group (CS). However, the HT group showed higher levels of these amino acids than the CT group. No difference in body weight evolution was apparent among the groups until the end of the eighth week of training. Nevertheless, on the ninth week the trained groups showed significantly lower weights than group CS. There were no significant differences, among all groups studied, in the weight, the content and concentration of both gastrocnemius and soleus muscles, and serum IGF1 levels, as well as the degradation rate of proteins in the gastrocnemius muscle. The content and concentration of DNA in the gastrocnemius were significantly lower in both groups fed HPSL (HS and HT), regardless of physical activity, than in the groups fed intact protein (CS, IS, CT and IT). The rate of protein synthesis in both gastrocnemius and soleus muscles were also lower in the HT group than those found in the CS, IS and HS groups. However, there was no difference when compared to those of the IT and CT groups. Summarizing, the HT group stood out because of its lower demand for new protein synthesis and amino acid utilization from the serum pool, consequently decreasing the need for higher amount of cellular DNA in the gastrocnemius muscle. Even so, this group kept the same muscle mass, protein content and concentration, as those of the other groups. These results suggest that the consumption of hydrolyzed milk whey protein may contribute to the preservation of the gastrocnemius muscle when associated with physical activity of endurance.
Mestrado
Nutrição Experimental e Aplicada à Tecnologia de Alimentos
Mestre em Alimentos e Nutrição
7
Temprano, López Ana. "The lipin protein family in human adipocytes: lipid metabolism and obesity." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/398025.
Full textAbstract:
Les lipins són una família conservada evolutivament de fosfatases de fosfatidat (PAP1) dependents de Mg2+, que generen diacilglicerol per a la síntesi de fosfolípids i triacilglicerol. En mamífers, la família consta de lipina-1, lipina-2 i lipina-3. Mentre en ratolins la mutació del gen Lpin1 causa lipodistròfia, les mutacions deletèries en el gen LPIN1 en humans no afecten la distribució del greix. No obstant, persones amb diabetis tipus 2 mostren nivells reduïts de l'expressió de LPIN1 i de l'activitat PAP1. Aquesta tesi estudia el paper de les lipins en el teixit adipós humà, la adipogènesi i la lipòlisi. Descobrim que la expressió de gens i proteïnes lipin és alterada en el teixit adipós de les persones amb diabetis tipus 2. Silenciant cada membre de la família lipin en la línia cel•lular humana de preadipòcits del síndrome Simpson-Golabi-Behmel (SGBS), mostrem que mentre que els tres membres tenen un paper en el primers estadis de l’adipogènesi, els preadipòcits silenciats de lipin es diferencien i acumulen lípids neutres, la qual cosa condueix a la hipòtesi de l'existència de vies alternatives per a la síntesi de triacilglicerol en adipòcits humans quan es reprimeix l'expressió de les lipin. Les lipin participen també en el reciclatge d'àcids grassos alliberats mitjançant la via lipolítica. Després de la inducció de la lipòlisi, les lipines són defosforilades i es desplacen a la membrana del reticle endoplasmàtic, on exerceixen la seva funció enzimàtica. Aquesta activació és induïda pels àcids grassos alliberats i s'inverteix amb la presència d’albúmina o triacsin C. La inducció d’adipòcits silenciats de cada lipina demostra el seu paper en el metabolisme dels lípids neutres. En resum, les lipin semblen no tenir un paper imprescindible en la adipogènesi humana però sí poden comprometre el reciclatge d'àcids grassos, important per a la homeòstasis lipídica.Las lipinas son una familia de fosfatasas de fosfatidato (PAP1) dependientes de Mg2+ evolutivamente conservadas, que generan diacilglicerol para la síntesis de fosfolípidos y triacilglicerol. En mamíferos, la familia consiste en lipina-1, lipina-2, y lipina-3. Mientras en ratones la mutación del gen Lpin1 causa lipodistrofia, las mutaciones deletéreas en el gen LPIN1 en humanos no afectan a la distribución de grasa. Sin embargo, los individuos con diabetes tipo 2 manifiestan niveles reducidos de expresión de LPIN1 y de actividad PAP1. En esta tesis doctoral se estudia la función de las lipinas en el tejido adiposo humano, la adipogénesis y la lipólisis. Descubrimos que la expresión génica y proteica de las lipinas está alterada en el tejido adiposo de individuos con diabetes tipo 2. La depleción de cada miembro de las lipinas en la línea celular humana de preadipocitos del síndrome Simpson–Golabi–Behmel (SGBS), mostró que, a pesar de que los tres miembros tienen un papel en la adipogénesis temprana, los adipocitos deplecionados de lipinas se diferencian y acumulan lípidos neutros, llevándonos a la hipótesis de la existencia de vías alternativas para la síntesis de triacilglicerol en adipocitos humanos cuando la expresión de las lipinas es reprimida. Las lipinas también intervienen en el reciclaje de los ácidos grasos liberados por la vía lipolítica. Tras la inducción de la lipólisis, las lipinas son defosforiladas y se desplazan a la membrana del retículo endoplásmico, donde ejercen su función. Esta activación es inducida por los ácidos grasos liberados, y revertida con albúmina o triacsin C. La depleción de cada lipina en adipocitos SGBS y posterior inducción de la lipólisis, demuestra su papel en el metabolismo de lípidos neutros. En resumen, las lipinas parecen no tener un papel indispensable en la adipogénesis humana pero sí comprometer el reciclaje de ácidos grasos, importante para la homeostasis lipídica.
Lipins are evolutionarily conserved Mg2+-dependent phosphatidate phosphatases (PAP1) that generate diacylglycerol for phospholipid and triacylglycerol synthesis. In mammals the Lipin family consists of lipin-1, lipin-2 and lipin-3. Whereas mutations in the Lpin1 gene cause lipodystrophy in mouse models, LPIN1 deleterious mutations in humans do not affect fat distribution. However, reduced LPIN1 expression and PAP1 activity have been described in participants with type 2 diabetes. In this doctoral thesis we investigate the roles of all lipin family members in human adipose tissue, adipogenesis and lipolysis. We found that adipose tissue gene and protein expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson–Golabi–Behmel syndrome (SGBS) pre-adipocyte cell line showed that even though all members alter early stages of adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids, pointing to the hypothesis of alternative pathways for triacylglycerol synthesis under repression of lipin expression. Lipins also have a role in the recycling of the fatty acids released by the lipolytic pathway. They become dephosphorylated upon lipolytic induction, and translocate to their active site, the endoplasmic reticulum membrane. This activation is induced by fatty acids and reversed with albumin or triacsin C. Depletion of every lipin member and subsequently stimulation of lipolysis in SGBS adipocytes revealed a role for lipins in neutral lipid metabolism. Overall, our data support that lipins may not have an indispensable role in adipogenesis, but their depletion compromise fatty acid recycling and lipid homeostasis.
8
Ainsworth, Julia. "Comparison of p53 and MAGI-3 regulation mediated by the E6 protein from high-risk human papillomavirus types 18 and 33." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112368.
Full textAbstract:
The HPV E6-p53 interaction is well-understood, but not for all high-risk HPV types. In addition, HPV E6 p53-independent functions are gaining recognition for their importance in cellular transformation but require clarification. Thus, the aim of this study was two-fold: (1) to gain insight into the p53-E6 interaction for high-risk HPV-33 and, (2) to explore how high-risk HPV E6 proteins targets cellular MAGI-3 for degradation.In vivo and in vitro results indicated that E6 from HPV types 18 and 33 interacted similarly with p53 although, variants of the HPV-33 E6 prototype demonstrated interesting disparities. Of note was HPV-33 E6 variant 2, which degraded p53 more efficiently than prototype HPV-33 E6 and HPV-18 E6. The E6 protein from HPV types 18 and 33 also potently degraded MAGI-3 via a different pathway than that used for p53. Specifically, proteasome inhibition did not interfere with MAGI-3 degradation and MAGI-3 was not ubiquitinated in the presence of the E6 protein.
Therefore, the results described herein enhance our understanding of high-risk HPV type 33 E6 and the E6-MAGI-3 interaction.
9
Salomão, Emilianne Miguel. "Atividade fisica associada ao crescimento tumoral e suplementação nutricional : estudo experimental em ratos jovens portadores do carcinossarcoma de Walker 256." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314509.
Full textAbstract:
Orientador: Maria Cristina Gomes MarcondesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo : A intensa mobilização de substratos dos tecidos da carcaça do hospedeiro, em função do crescimento neoplásico, promove no organismo o estado caracterizado como caquexia. Presente na maioria dos pacientes com câncer, a caquexia promove intensa perda involuntária de peso decorrente, preferencialmente, da depleção da proteína muscular em função do aumento da degradação e/ou da diminuição da síntese protéica, culminando na redução da qualidade e expectativa de vida. Trabalhos têm mostrado que o desenvolvimento do câncer dá-se de forma mais agressiva e severa quanto mais jovem for o paciente. Considerando-se que: a) os aminoácidos de cadeia ramificada, principalmente a leucina, participam ativamente na sinalização celular, estimulando a síntese como também inibindo a degradação protéica; b) a glutamina, aminoácido não essencial, participa indiretamente no aumento da síntese protéica muscular esquelética, como também da diminuição do catabolismo protéico; c) o exercício físico exerce grande estimulação da síntese protéica; temos por principal interesse, neste trabalho, minimizar as alterações metabólicas do tecido hospedeiro frente ao crescimento neoplásico. Assim, associando-se a suplementação nutricional de leucina e/ou glutamina e exercício físico aeróbio, de intensidade leve a moderada, ao crescimento do carcinossarcoma de Walker 256, avaliamos a composição corpórea, o metabolismo protéico do músculo gastrocnêmio, o estresse oxidativo e o perfil sérico (proteína, albumina, globulina, glicose, lípedes totais, colesterol total, colesterol HDL, triacilgliceróis e lactato) em ratos Wistar em pleno desenvolvimento corporal. Nossa tentativa foi, com a suplementação nutricional aliada ao exercício, prevenir ou atenuar o estado caquético do animal conseqüente a evolução tumoral. Os resultados mostraram que os grupos inoculados com tumor apresentaram redução do peso corpóreo e da ingestão alimentar no final dos experimentos. Verificamos alterações na composição corpórea química, tais como, elevado teor de água corpórea, redução do teor de gordura total e diminuição do nitrogênio colageno da carcaça nos ratos implantados com tumor de Walker 256. Houve, ainda, diminuição da síntese e aumento da degradação no músculo gastrocnêmio nos animais implantados com tumor. Além disso, observou-se aumento do conteúdo de malondialdeído (MDA), em relação ao conteúdo de antioxidantes como GST, nos músculos gastrocnêmio e cardíaco indicando aumento do estresse oxidativo associado à evolução tumoral. Observamos também, redução dos teores séricos de proteína, albumina, glicose, colesterol e HDL nesses animais portadores de tumor. A associação suplementação nutricional/exercício promoveu melhora no estado caquético dos animais, visto que provocou: ligeira melhora da eficiência alimentar; preservação de proteína total da carcaça, manutenção da incorporação de fenilalanina e menor degradação da proteína muscular no grupo suplementado com leucina, além de preservar a proteína total sérica, manutenção da glicemia, colesterol total sérico e reduzir o lactato sérico, principalmente no grupo suplementado com leucina. Esses dados sugerem que o efeito benéfico da associação entre suplementação nutricional e exercício ao crescimento neoplásico foi pouco pronunciado, provavelmente, ao fato do crescimento acelerado do tumor superar as adaptações ao programa de treinamento físico
Abstract: The intense nutrients mobilisation of the host carcass tissue, in function of the neoplastic growth, leads to the host cachexia. Present in most of the patients with cancer, the cachexia is the state characterized by the involuntary weight loss that overtakes the protein muscle depletion increasing the degradation and/or decreasing the protein synthesis process in the muscle. In these cases, there is reduction of the quality and the life expectancy. On the other hand, some studies have shown that the development of the cancer is more aggressive and severe in younger patients. The branched-chain amino acids (BCAA), especially leucine, actively participate on cell signalling, stimulating the synthesis as well as inhibiting the protein degradation. The glutamine, a non essential amino acid, indirectly activates the muscle protein synthesis, as well as inhibits the protein catabolism. Additionally, the physical exercise stimulates the protein synthesis. Knowing these facts, our main interests, were to minimize the metabolic alterations in tumor-bearing host. The nutritional supplementation of leucine and/or glutamine and moderate aerobic exercise associated to the Walker 256 tumor growth could avoid the muscular depletion, preserve the protein body mass and the energetic source, possibly preventing the cachetic state of the animal. For this purpose, we evaluated the body chemical composition, the protein metabolism, measuring the muscle protein synthesis and catabolism, as well as the oxidative stress and biochemical blood profile in young tumor-bearing rats. The results showed reduced body weight and food intake in tumorbearing rats. The tumor effects changed the chemical body composition, showing high body water content, reduced total body fat and low carcass nitrogen in Walker tumor bearing rats. Protein synthesis was reduced and proteolysis was increased in young tumor-bearing rats. Additionally, the malondyhaldeide content increased in skeletal and cardiac muscle suggesting high oxidative stress associated to the tumor development. We observed low blood protein, albumin, globulin, glucose and cholesterol in tumor-bearing rats. The improvement of the cachexia was less pronounced in tumor-bearing animal which received supplemented diet associated to physical exercise. In these groups, we verified that food efficiency was slightly increased in comparison to the non-exercised tumour-bearing group. The carcass protein was maintained as well as the phenylalanine incorporation in muscle and less tyrosine was released from skeletal muscle when tumour-bearing groups were fed leucine rich diet. In these groups, the total blood protein, glycemia, total blood cholesterol and reduced blood lactate were preserved, mainly in exercised group. Those data suggest that the beneficial effect of the association among amino acids rich diet, exercise and tumor growth was not so expressive, probably due to the exponential tumor growth overcame the physical training program
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
10
Liste, Calleja Leticia. "Study and characterisation of human HEK293 cell line as a platform for recombinant protein production." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/308324.
Full textAbstract:
El
present
treball
es
centra
en
l’estudi
de
la
producció
de
proteïnes
recombinants
en
línies
cel·∙lulars
de
mamífer.
Concretament,
s’ha
realitzat
l’estudi
de
tres
estratègies
de
bioprocés,
totes
elles
basades
en
el
cultiu
de
cèl·∙lules
HEK293.
Com
a
proteïna
model
per
a
l’expressió
de
proteïnes
heteròlogues
s’ha
triat
la
proteïna
CapPCV2,
la
qual
conforma
la
càpsida
viral
del
Circovirus
porcí
serotip
2
(PCV2).
Aquest
virus
és
l’agent
causal
de
PCVDS
(porcine
circovirus
diseases
o
malaties
derivades
de
circovirus
porcí).
Aquest
terme
engloba
un
conjunt
de
malalties
i
síndromes
que
tenen
un
elevat
impacte
econòmic
en
la
indústria
porcina.
El
projecte
s’ha
enfocat
des
de
la
perspectiva
de
desenvolupament
i
optimització
del
bioprocés
i,
en
conseqüència,
l’increment
de
la
producció
volumètrica
ha
estat
la
força
impulsora
de
tot
el
treball.
En
primer
lloc
es
presenten
els
estudis
per
a
la
selecció
del
medi
de
cultiu
i
suplements
nutricionals.
El
creixement
cel·∙lular
depèn
en
gran
mesura
de
les
característiques
nutricionals
i
fisicoquímiques
del
medi
en
que
se
les
cultiva.
Per
tant,
trobar
el
medi
adequat
és
un
dels
factors
clau
per
a
l’expansió
del
cultiu
cel·∙lular.
L’estudi
inicial
de
medis
de
cultiu
va
permetre
augmentar
sis
vegades
la
densitat
de
cèl·∙lules
viables
en
comparació
al
medi
original
en
que
es
cultivaven.
D’altra
banda,
s’han
explorat
diferents
estratègies
de
cultiu,
i
com
a
resultat
s’ha
implementat
una
estratègia
de
fed-‐batch
que
ha
permès
arribar
a
densitats
cel·∙lulars
de
26.8x106
cell/mL.
En
el
segon
i
tercer
capítol
de
resultats,
s’avaluen
tres
estratègies
diferents
per
a
la
producció
de
la
proteïna
recombinant
CapPCV2
(r-‐CapPCV2).
La
primera
estratègia
ha
estat
la
infecció
de
cèl·∙lules
HEK293
amb
un
vector
adenoviral
que
codifica
el
gen
de
la
CapPCV2
(vector
generat
dins
del
treball
d’aquesta
tesis
doctoral).
Els
paràmetres
d’infecció
s’han
estudiat
en
profunditat
per
tal
de
trobar
els
paràmetres
d’infecció
(medi
de
cultiu,
MOI
(multiplicitat
d’infecció),
TOI
(temps
d’infecció)
i
TOH
(temps
de
recollida))
per
a
la
millora
de
la
producció
de
la
proteïna
i
el
vector
adenoviral.
La
segona
i
tercera
estratègia
estan
basades
en
la
generació
de
línies
cel·∙lulars
estables.
Concretament,
s’ha
generat
una
línia
cel·∙lular
productora
de
r-‐CapPCV2
a
partir
de
la
integració
a
l’atzar
del
vector
plasmídic
en
el
genoma
de
la
cèl·∙lula.
D’altra
banda,
s’han
generat
línies
cel·∙lulars
amb
la
integració
dirigida
del
gen
en
llocs
prèviament
caracteritzats
com
d’altra
transcripció
genètica.
La
integració
dirigida
s’ha efectuat
mitjançant
la
tecnologia
RMCE
(recombinant
mediated
cassette
exchange,
o
bescanvi
de
casset
mitjançada
per
recombinació).
Després
de
la
comparació
de
les
productivitats
específiques
i
volumètriques
aconseguides
amb
cada
estratègia,
el
millor
productor
va
ser
seleccionat.
Nogensmenys,
r-‐CapPCV2
es
produeix
en
quantitats
molt
baixes
i
per
tant
no
ha
sigut
possible
dissenyar
un
procés
de
producció
rentable
i
altres
alternatives
de
producció
s’haurien
d’estudiar
en
un
futur.
Finalment,
l’estudi
d’un
comportament
metabòlic
particular
observat
en
les
cèl.lules
en
cultiu
s’ha
adreçat
des
d’una
perspectiva
fisiològica
i
metabòlica.
A
certes
condicions
extracel·∙lulars,
s’ha
observat
que
les
cèl·∙lules
HEK293
poden
consumir
de
manera
simultània
glucosa
i
lactat
durant
el
seu
creixement
exponencial.
Després
d’un
ampli
estudi
d’aquestes
condicions,
s’ha
determinat
que
el
canvi
de
la
producció
d’àcid
làctic
(que
és
el
principal
problema
dels
cultius
d’alta
densitat
de
cèl·∙lules
de
mamífer)
cap
al
consum
d’aquest
metabòlit
pot
ser
generat
des
de
el
començament
del
cultiu
quan
el
pH
és
de
6.6
i
la
concentració
de
lactat
és
de
4-‐8mM.
En
aquestes
condicions,
ni
el
creixement
cel·∙lular
ni
la
producció
de
proteïna
es
veuen
afectades
negativament.
A
la
llum
d’aquests
resultats,
es
genera
la
hipòtesi
de
que
les
cèl·∙lules
HEK293
poden
co-‐transportar
el
lactat
extracel.lular
i
els
protons
com
un
mecanisme
de
detoxificació
del
pH.
D’altra
banda,
l’aplicació
de
l’anàlisi
de
balanç
de
fluxos
(FBA)
ha
revelat
que
quan
la
glucosa
i
el
lactat
es
consumeixen
simultàniament
s’aconsegueix
un
metabolisme
“equilibrat”,
és
a
dir
els
fluxos
de
la
glicòlisi
i
el
cicle
TCA
esdevenen
similars,
evitant
l’acumulació
de
piruvat
en
el
citosol,
la
seva
transformació
a
làctic
i
finalment
la
secreció
d’aquest
metabòlit.
Aquest
comportament
és
totalment
oposat
al
que
s’observa
de
forma
general
en
els
cultius
de
cèl.lules
de
mamífer
en
creixement
exponencial,
on
els
elevats
fluxos
de
la
glicòlisi
troben
una
limitació
en
els
fluxos
d’entrada
a
la
mitocòndria
(és
a
dir,
del
cicle
TCA)
i
conseqüentment
el
lactat
és
produït
i
secretat
al
medi.
La
construcció
d’un
model
metabòlic
i
l’aplicació
de
FBA
permetrà
fer
prediccions
in
silico
de
comportaments
metabòlics
causats
per
la
sobreexpressió
o
el
silenciament
de
gens
diana.
Aquesta
estratègia
obre
la
possibilitat
de
generar
línies
cel·∙lulars
que
presentin
un
metabolisme
optimitzat
per
tal
d’estudiar
estratègies
de
cultiu
més
eficients
per
a
l’increment
de
la
densitat
cel·∙lular
i
productivitat
de
proteïna
recombinant.The thesis is focused on the study of recombinant protein production in mammalian cell lines. In particular, the study of three different approaches of different bioprocesses based on HEK293 cells has been addressed. As a model protein for recombinant expression, CapPCV2 has been selected. This protein makes up the viral capsid of Porcine circovirus serotype 2 (PCV2), which is the causative agent of PCVDs (porcine circovirus diseases), a group of diseases with major impact in pig’s industry worldwide. This project has been addressed from the perspective of bioprocess development and optimization and therefore, the increment of volumetric production of cells, virus and proteins have been the driving force of the research. Firstly, cell culture media and nutritional supplementation studies are presented. Cell growth relies in high extent to the nutritional and physicochemical characteristics of the media in which cells are cultured and therefore, finding the proper cell media is one of the key factors for cell culture expansion. The initial media study resulted in a 6-‐fold increment of the maximal viable cell achieved in the original media. Besides, different cell culture strategies have been explored, which resulted in a fed-‐batch strategy that allowed reaching maximal viable cell densities of 26.8x106 cell/mL, which represents 13-‐fold increment on maximal viable cell density originally reached. In the second and third chapter of results, three different approaches for the expression of recombinant CapPCV2 (r-‐CapPCV2) are evaluated and discussed. As a first approach, a viral recombinant adenovirus encoding for the gene CapPCV2 has been generated and used as viral vector for the production of the recombinant protein in HEK293 cells. Besides, a deep study of the main parameters that affect the infection performance has been carried out and discussed in order to find the best media, MOI (multiplicity of infection), TOI (time of infection) and TOH (time of harvest) for adenovirus and recombinant protein production. This study was performed with an adenovirus expressing the reporter gene GFP and thereafter, the best infection parameters encountered were applied for the production of r-‐CapPCV2 (media: SFMTransFx-‐293 supplemented with 4mM glutaMAX, 5% FBS and 10%CB5; MOI:1; TOI:1x106 cell/mL) and TOH:48hpi). The second and third strategies are both based on the generation of stable producer cell lines, but one strategy relies on illegitimate (or random) integration of the gene in the HEK293 genome ,whereas the other strategy is a site-‐directed integration of the gene in previously characterized hot-‐spots (i.e. high-‐active transcribed regions from genome). The site-‐directed integration was performed using RMCE technology (Recombinant mediated cassette exchange). After the comparison of the specific and volumetric productivities achieved with each approach, the best producer has been selected. Nevertheless, r-‐CapPCV2 was poorly produced so it was unfeasible to develop/design a cost-‐effective industrial bioprocess and other alternatives must be studied in the future. Finally, the study of an unexpected metabolic behaviour observed in HEK293 cells cultured in our lab has been addressed from a physiologic and metabolic perspective. HEK293 cells could concomitantly consume glucose and lactate in exponentially growing cultures at particular environmental conditions. After a deep study of these conditions, it was found out that the switch from lactate secretion (which is the main drawback of mammalian high cell density cultures) to lactate consumption can be triggered from the beginning of cell culture at pH0=6.6 together with the addition of 4-‐12mM of lactate to media. Remarkably, under these conditions nor cell growth neither protein production were negatively affected. Form these results, we hypothesize that HEK293 can co-‐transport lactate and H+ to the cytosol as a pH-‐detoxification mechanism. Moreover, the application of flux balance analysis permitted to find out that when lactate and glucose are consumed together a “more balanced” metabolism is achieved, meaning that glycolytic and TCA fluxes became similar, avoiding pyruvate accumulation at the cytosol and consequently, lactate formation. This is totally opposed to the extensively observed metabolism of exponentially growing mammalian cell lines, where the high flux through the glycolytic pathway encounters a limitation on the fluxes entering the mitochondria (hence, the TCA cycle) and consequently lactate is produced and secreted to media. The construction of a HEK293 metabolic model and the application of FBA will allow making in silico predictions of metabolic beahaviours after the upregulation or downregulation of target genes. This strategy may open the possibility of generate engineered HEK293 cell lines with an optimised metabolism in order to study more efficient cell culture strategies towards the achievement of higher cell densities and product titres.
Books on the topic "Protein metabolsim"
2
Welle, Stephen. Human Protein Metabolism. New York, NY: Springer New York, 1999. http://dx.doi.org/10.1007/978-1-4612-1458-8.
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4
Ferraiolo, Bobbe L., Marjorie A. Mohler, and Carol A. Gloff, eds. Protein Pharmacokinetics and Metabolism. Boston, MA: Springer US, 1992. http://dx.doi.org/10.1007/978-1-4899-2329-5.
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5
Wapnir, Raul A. Protein nutrition and mineral absorption. Boca Raton, Fla: CRC Press, 1990.
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6
Protein homeostasis. Cold Spring Harbor, N.Y: Cold Spring Harbor Laboratory Press, 2011.
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7
Mayer, R. J., Martin Rechsteiner, and Aaron J. Ciechanover. Protein degradation. Weinheim: Wiley-VCH, 2007.
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10
Posttranslational modification of proteins: Expanding nature's inventory. Englewood, Colo: Roberts and Co. Publishers, 2006.
Find full textBook chapters on the topic "Protein metabolsim"
1
Poortmans, J. R. "Protein Metabolism." In Principles of Exercise Biochemistry, 227–78. Basel: KARGER, 2003. http://dx.doi.org/10.1159/000074370.
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2
Norberg, Åke, Felix Liebau, and Jan Wernerman. "Protein Metabolism." In The Stress Response of Critical Illness: Metabolic and Hormonal Aspects, 95–106. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-27687-8_9.
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3
Griminger, P., and C. G. Scanes. "Protein Metabolism." In Avian Physiology, 326–44. New York, NY: Springer New York, 1986. http://dx.doi.org/10.1007/978-1-4612-4862-0_14.
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4
Miller, Benjamin F., and Matthew M. Robinson. "Metabolism, Protein." In Encyclopedia of Exercise Medicine in Health and Disease, 576–79. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-540-29807-6_131.
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Kowaltowski, Alicia, and Fernando Abdulkader. "Protein Metabolism." In Where Does All That Food Go?, 67–78. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-50968-2_6.
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Lefebvre, Cedric W., Jay P. Babich, James H. Grendell, James H. Grendell, John E. Heffner, Ronan Thibault, Claude Pichard, et al. "Protein Metabolism." In Encyclopedia of Intensive Care Medicine, 1862–65. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-00418-6_746.
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7
Welle, Stephen. "The Importance of Protein Dynamics." In Human Protein Metabolism, 1–10. New York, NY: Springer New York, 1999. http://dx.doi.org/10.1007/978-1-4612-1458-8_1.
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Welle, Stephen. "Basic Mechanisms of Protein Turnover." In Human Protein Metabolism, 11–28. New York, NY: Springer New York, 1999. http://dx.doi.org/10.1007/978-1-4612-1458-8_2.
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Welle, Stephen. "Methods for Studying Protein Metabolism in Humans." In Human Protein Metabolism, 29–71. New York, NY: Springer New York, 1999. http://dx.doi.org/10.1007/978-1-4612-1458-8_3.
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Welle, Stephen. "Normative Data from Infancy to Old Age." In Human Protein Metabolism, 72–90. New York, NY: Springer New York, 1999. http://dx.doi.org/10.1007/978-1-4612-1458-8_4.
Full textConference papers on the topic "Protein metabolsim"
1
El-fadl, Rihab, Nasser Rizk, Amena Fadel, and Abdelrahman El Gamal. "The Profile of Hepatic Gene Expression of Glucose Metabolism in Mice on High Fat Diet." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0213.
Full textAbstract:
Obesity is a growing problem worldwide, and recent data indicated that 20% of the populations would be obese. Obesity arises as a multifactorial disease caused by inherited traits that interact with lifestyle factors such as diet and physical activity. The liver plays an essential role in the gluco-regulation via regulating glucose, lipid and protein metabolism. The process of glucose metabolism is controlled by a range of molecular mechanisms and genes which affect the metabolism of the liver during intake of high fat diet (HFD). The objective of this research is to investigate the profile of hepatic gene expression of glucose metabolism in mice on HFD treated with leptin (5 mg/kg BW Ip injection). Ten wild type CD1 mice fed on HFD is used for this study, where groups are control (vehicle - leptin) and test group (vehicle + leptin). Body weight (BW) was measured, and blood chemistry, insulin and leptin were measured at the end of the experiments. Total RNA was isolated from the liver tissue, and RTPCR profiler array technology was used to evaluate the mRNA expression of 84 essential genes of hepatic glucose metabolism. The data of the BW and blood chemistry are not significantly different between the two groups. Leptin treatment enhanced the metabolic pathways and the candidate genes of the different metabolic pathway; glycogen metabolism such as Gys1, Gys2 and Pygm, pentose phosphate shunt such as Rpia and suppressed the glycolysis such as Aldob, and TCA cycle such as Mdh1b. In conclusion, this study has shown that leptin could affect the profile of the hepatic mouse genes of glucose metabolism in the early stages of HFD to induce obesity
2
Chiang, T. M., R. J. H. Wojcikiewicz, A. H. Kang, and J. N. Fain. "PHOSPHORYLATION OF THE OUTER SURFACE OF PLATELETS ENHANCES THE EFFECTS OF COLLAGEN ON PLATELET AGGREGATION, ATP RELEASE, CALCIUM TRANSLOCATION AND PHOSPHOINOSITIDE HYDROLYSIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644477.
Full textAbstract:
We have recently isolated and purified from human plasma two isomeric forms of protein kinase, both of which can phosphorylate the outer surface proteins of human platelets. One of the proteins phosphorylated is the platelet collagen receptor. The phosphorylation of the outer surface proteins of human platelets increased their functional responsiveness to collagen. Collagen-stimulated platelet aggregation, release of ATP and calcium translocation were all enhanced by pretreatment with plasma protein kinase in the presence of ATP. The mechanism by which phosphorylated platelets become hypersensitive to collagen is not established. In the present study, we have used [3H]myo-inositol-labeled human platelets to investigate the possible role of phosphoinositide metabolism in mediating this hypersensitivity. Formation of inositol mono-, bis-, and trisphosphate in response to collagen was more pronounced in phosphorylated platelets than controls. these results indicate that enhanced phosphoinositide hydrolysis in phosphorylated platelets correlate with the increased functional responses to collagen.
3
Sauvant, D., and P. Nozière. "The rumen protein balance as a key trait to model ruminant responses to dietary proteins." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_142.
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Vandaele, L., K. Goossens, J. De Boever, and S. De Campeneere. "Several roads lead to Rome: about improving nitrogen efficiency in cattle." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_1.
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Andreini, E. M., S. M. Augenstein, C. S. Fales, R. D. Sainz, and J. W. Oltjen. "Effects of feeding level on efficiency of high and low residual feed intake beef steers." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_10.
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Silva, D. L., B. R. Carvalho, H. C. Ferreira Júnior, H. C. Oliveira, L. F. T. Albino, H. S. Rostagno, J. E. Pettigrew, S. E. F. Guimarães, and M. I. Hannas. "Sources and levels of zinc affect the expression of genes involved in broiler lipid metabolism." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_100.
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Lourenço, M., K. Buyse, B. Wegge, L. Goethals, G. G. P. Janssens, and E. Delezie. "Effect of hydrolysable tannins on protein and energy efficiency in laying hens." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_101.
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Miranda, A. C. T., D. M. Ramos, F. N. Godoi, F. G. F. Padilha, G. C. Peixoto, A. Galina, and F. Q. Almeida. "Muscular mitochondrial respirometry in training horses." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_102.
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Serviento, A. M., E. Merlot, A. Prunier, H. Quesnel, I. Louveau, B. Lebret, and D. Renaudeau. "Heat stress in pregnant sows: effects on growth performance and carcass composition of the offspring." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_103.
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Campos, P. H. R. F., N. Le Floc’h, D. Renaudeau, J. Noblet, and E. Labussière. "Effects of lipopolysaccharide-induced fever on metabolic heat production." In 6th EAAP International Symposium on Energy and Protein Metabolism and Nutrition. The Netherlands: Wageningen Academic Publishers, 2019. http://dx.doi.org/10.3920/978-90-8686-891-9_104.
Full textReports on the topic "Protein metabolsim"
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Ohlrogge, J. B. Role of acyl carrier protein isoforms in plant lipid metabolism: Progress report. Office of Scientific and Technical Information (OSTI), January 1989. http://dx.doi.org/10.2172/6210587.
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Halim, Nader. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy. Fort Belvoir, VA: Defense Technical Information Center, March 2007. http://dx.doi.org/10.21236/ad1013984.
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Hanke, Andreas. Regulation of DNA Metabolism by DNA-Binding Proteins Probed by Single Molecule Spectroscopy. Fort Belvoir, VA: Defense Technical Information Center, December 2006. http://dx.doi.org/10.21236/ada459264.
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Reue, K., S. Rehnmark, R. D. Cohen, T. H. Leete, M. H. Doolittle, C. S. Giometti, K. Mishler, and B. G. Slavin. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression. Office of Scientific and Technical Information (OSTI), July 1997. http://dx.doi.org/10.2172/505325.
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Tiedje, James M. Integrated Analysis of Protein Complexes and Regulatory Networks Involved in Anaerobic Energy Metabolism of Shewanella Oneidensis MR-1. Office of Scientific and Technical Information (OSTI), June 2005. http://dx.doi.org/10.2172/893447.
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Boyer, Bert B. Molecular Mechanisms of Metabolic Suppression: Protein Synthesis and Mitochondrial Respiration in a Hibernating Ground Squirrel Model. Fort Belvoir, VA: Defense Technical Information Center, June 2005. http://dx.doi.org/10.21236/ada435855.
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Sukumar, Saraswati. Imaging the Vascular and Metabolic Impact of Claudin-7, a Tight Junction Protein in Transgenic Human Breast Cancer Models. Fort Belvoir, VA: Defense Technical Information Center, June 2002. http://dx.doi.org/10.21236/ada410196.
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Aleksandrov, V. A., L. N. Shilova, A. V. Aleksandrov, N. I. Emelianov, N. V. Aleksandrova, N. V. Nikitina, E. E. Mozgovaya, and I. A. Zborovskaya. THE STUDY OF THE INFLUENCE OF ANGIOOPETIN-LIKE PROTEIN TYPE 4 ON THE INFLAMMATORY AND METABOLIC PROCESSES IN RHEUMATOID ARTHRITIS. Media Sphere, 2019. http://dx.doi.org/10.18411/2305-2198-2019-1-9-10.
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Yang, Jia-ming, Yun Luo, Jia-hong Zhang, Qin-qin Liu, Qiang Zhu, Hua Ye, Yan-long Niu, et al. Effects of WB-EMS and Protein Supplementation on Body Composition, Physical Function, Metabolism and Inflammatory Biomarkers in Middle-Aged and Elderly Patients with Sarcopenic Obesity: A Meta-Analysis of Randomized Controlled Trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, September 2021. http://dx.doi.org/10.37766/inplasy2021.9.0096.
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Role of acyl carrier protein isoforms in plant lipid metabolism. Office of Scientific and Technical Information (OSTI), January 1990. http://dx.doi.org/10.2172/7138275.
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