Academic literature on the topic 'Extracellular oxidative metabolism'

Abstract. Soil heterotrophic respiration is a major determinant of the carbon (C) cycle and its interactions with climate. Given the complexity of the respiratory machinery, it is traditionally considered that oxidation of organic C into carbon dioxide (CO2) strictly results from intracellular metabolic processes. Here we show that C mineralization can operate in soils deprived of all observable cellular forms. Moreover, the process responsible for CO2 emissions in sterilized soils induced a strong C isotope fractionation (up to 50 ‰) incompatible with respiration of cellular origin. The supply of 13C glucose in sterilized soil led to the release of 13CO2 suggesting the presence of respiratory-like metabolism (glycolysis, decarboxylation reaction, chain of electron transfer) carried out by soil-stabilized enzymes, and by soil mineral and metal catalysts. These findings indicate that CO2 emissions from soils can have two origins: (1) from the well-known respiration of soil heterotrophic microorganisms and (2) from an extracellular oxidative metabolism (EXOMET) or, at least, catabolism. These two metabolisms should be considered separately when studying effects of environmental factors on the C cycle because the likelihood is that they do not obey the same laws and they respond differently to abiotic factors.

Alterations in neutrophil function by tobacco products may play a central role in the pathogenesis of periodontal diseases and several smoking-related systemic diseases. The aim of the study was to evaluate the effect of smoking on neutrophil oxidative metabolism. Materials and methods. The study included 17 smoking men free of systemic diseases who were referred for treatment of various odontological diseases to outpatient department of Kaunas University of Medicine Hospital. The age of subjects varied from 22 to 43 years. All subjects answered the questions about smoking habits. Clinical examination included assessment of oral hygiene status according to the OHI-s index and periodontal status according to Russell and Ramfjord indices. To evaluate the oxidative metabolism of neutrophils, luminol- and liucigenin-dependent chemiluminescence and nitroblue tetrazolium test were used. Results. After smoking, extracellular liucigenin-dependent chemiluminescence response was higher as compared to the response before smoking, but total (intra- and extracellular) luminol-dependent chemiluminescence response was the same both before and after smoking. Exposure of neutrophils to smoking caused a significant increase in nitroblue tetrazolium reduction. Conclusion. The release of reactive oxygen species in neutrophils exposed to smoking may alter the pathogenic processes in periodontal diseases.

Hormones and other extracellular agents often stimulate energy-requiring processes such as muscle contraction and secretion through increases in cytosolic calcium. To preserve energy homeostasis, ATP formation must also be stimulated. One important mechanism involves increases in mitochondrial calcium and activation of key steps in the process of oxidative phosphorylation.

Spermine was toxic to BHK-21/C13 cells in the absence of any extracellular metabolism of the amine. Inhibition of copper-containing amine oxidases with aminoguanidine partially prevented the response, whereas inhibition of polyamine oxidase with MDL-72,527 exacerbated the effect. Oxidation by an intracellular copper-containing amine oxidase may be involved in the toxicity of spermine, whereas the polyamine-interconversion pathway appears to play a cytoprotective role. There was no evidence for spermine imposing a state of oxidative stress within the cells. Inhibition of catalase and glutathione reductase did not alter the cytotoxicity of spermine, and there was no excretion of oxidized glutathione into the extracellular medium. The results suggest that spermine itself can exert a toxic effect directly on the cells.

Under physio-pathological conditions, cells release membrane-surrounded structures named Extracellular Vesicles (EVs), which convey their molecular cargo to neighboring or distant cells influencing their metabolism. Besides their involvement in the intercellular communication, EVs might represent a tool used by cells to eliminate unnecessary/toxic material. Here, we revised the literature exploring the link between EVs and redox biology. The first proof of this link derives from evidence demonstrating that EVs from healthy cells protect target cells from oxidative insults through the transfer of antioxidants. Oxidative stress conditions influence the release and the molecular cargo of EVs that, in turn, modulate the redox status of target cells. Oxidative stress-related EVs exert both beneficial or harmful effects, as they can carry antioxidants or ROS-generating enzymes and oxidized molecules. As mediators of cell-to-cell communication, EVs are also implicated in the pathophysiology of oxidative stress-related diseases. The review found evidence that numerous studies speculated on the role of EVs in redox signaling and oxidative stress-related pathologies, but few of them unraveled molecular mechanisms behind this complex link. Thus, the purpose of this review is to report and discuss this evidence, highlighting that the analysis of the molecular content of oxidative stress-released EVs (reminiscent of the redox status of originating cells), is a starting point for the use of EVs as diagnostic and therapeutic tools in oxidative stress-related diseases.

Reactive oxygen species (ROS) are a normal byproduct of cellular metabolism and are required components in cell signaling and immune responses. However, an imbalance of ROS can lead to oxidative stress in various pathological states. Increases in oxidative stress are one of the hallmarks in cancer cells, which display an altered metabolism when compared to corresponding normal cells. Extracellular superoxide dismutase (EcSOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide anion (O2−) in the extracellular environment. By doing so, this enzyme provides the cell with a defense against oxidative damage by contributing to redox balance. Interestingly, EcSOD expression has been found to be decreased in a variety of cancers, and this loss of expression may contribute to the development and progression of malignancies. In addition, recent compounds can increase EcSOD activity and expression, which has the potential for altering this redox signaling and cellular proliferation. This review will explore the role that EcSOD expression plays in cancer in order to better understand its potential as a tool for the detection, predicted outcomes and potential treatment of malignancies.

Background. Mongolian medical warm acupuncture has a desirable therapeutic effect on sciatica. Apoptosis of the nucleus pulposus cells is considered to play an important role in sciatica. Evidence has demonstrated that oxidative stress and its induced activation of the signaling pathways play important roles in sciatica. However, further research is expected to reveal whether Mongolian medical warm acupuncture can inhibit the apoptosis of nucleus pulposus cells and oxidative stress. Objective. To study the effect of the p38 MAPK pathway activated by the generated ROS on apoptosis and the expression of the genes related to the balance of the extracellular matrix metabolism during treatment of sciatica with Mongolian medical warm acupuncture. Method. The volume of the active oxygen generated in the nucleus pulposus cells was detected following intervention of Mongolian medical warm acupuncture. The p38 MAPK phosphorylation level was detected with Western blot. The genes are related to the metabolism of the nucleus pulposus extracellular matrix. Result. Mongolian medical warm acupuncture reduced the active oxygen within the nucleus pulposus cells and inhibited the activation of the p38 MAPK pathway (P=0.013). Meanwhile, it upregulated the gene expression of Type II collagen, aggrecan, Sox-9, and tissue matrix metalloproteinase reagent 1 (P-0.015; P=0.025; P=0.031; P=0.045) and downregulated the gene expression of matrix metalloproteinase 3 (P=0.015). Conclusion. Mongolian medical warm acupuncture may inhibit apoptosis of nucleus pulposus cells and activation of the extracellular matrix decomposition metabolism pathway and promote its anabolism. This process may rely on the oxidative stress matrix of the p38 MAPK pathway.

Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation.

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules, and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

Diet-induced obesity is associated with proteinuria and glomerular disease in humans and rodents. We have shown that in mice fed a high-fat diet, increased renal expression of the transcriptional factor sterol-regulatory element binding protein-1 (SREBP-1) plays a critical role in renal lipid accumulation and increases the activity of proinflammatory cytokines and profibrotic growth factors. In the current study, we have determined a key role of the farnesoid X receptor (FXR) in modulating renal SREBP-1 activity, glomerular lesions, and proteinuria. We found that feeding a Western-style diet to DBA/2J mice results in proteinuria, podocyte loss, mesangial expansion, renal lipid accumulation, and increased expression of proinflammatory factors, oxidative stress, and profibrotic growth factors. Treatment of these mice with the highly selective and potent FXR-activating ligand 6-α-ethyl-chenodeoxycholic acid (INT-747) ameliorates triglyceride accumulation by modulating fatty acid synthesis and oxidation, improves proteinuria, prevents podocyte loss, mesangial expansion, accumulation of extracellular matrix proteins, and increased expression of profibrotic growth factors and fibrosis markers, and modulates inflammation and oxidative stress. Our results therefore indicate that FXR activation could represent an effective therapy for treatment of abnormal renal lipid metabolism with associated inflammation, oxidative stress, and kidney pathology in patients affected by obesity.

Les reins sont les organes cibles de nombreuses molécules toxiques. Les cellules épithéliales du tubule proximal rénal sont particulièrement vulnérables vis-à-vis de xénobiotiques utilisés comme médicaments ou non. Ces agressions peuvent être corrélées à une augmentation du stress oxydatif et induire la mort cellulaire. Elles peuvent également mener à la perte des caractéristiques phénotypiques des cellules épithéliales, initiant leur dédifférenciation en cellules mésenchymateuses et éventuellement en fibroblastes, principaux responsables de la fibrose rénale.<p>Les stratégies de protection – notamment implémentées en clinique lors de l'administration de médicaments néphrotoxiques – reposant sur une approche pharmacologique restent rares.<p>A partir de données de médecines traditionnelles, nous avons sélectionné une série de plantes considérées utiles pour le traitement ou la prévention de troubles associés aux maladies rénales :Angelicae sinensis radix, Eleutherococci radix, Ginseng radix, Schisandrae chinensis fructus et Silybi mariani fructus.<p>A l'aide d'un modèle in vitro reposant sur l'emploi de la lignée cellulaire HK-2, nous avons examiné si ces produits pouvaient apporter une protection efficace vis-à-vis de 3 xénobiotiques néphrotoxiques :les acides aristolochiques, le cisplatine et la ciclosporine. Cinq phénomènes impliqués dans la néphrotoxicité et couramment retrouvés lors du développement de la fibrose rénale ont été investigués :(i) la mortalité cellulaire et l'apoptose ;(ii) la génération de stress oxydatif ;(iii) la modulation des capacités de régénération ;(iv) la production de matrice extracellulaire ;et (v) l'activation de la voie de signalisation de la β-caténine. <p>Parmi les 5 plantes étudiées sur ce modèle, celle présentant l'activité la plus intéressante vis-à-vis de l'un des 3 toxiques a été investiguée plus en détails afin d'identifier le(s) composé(s) responsable(s) de sa bioactivité. Les résultats ont indiqué que l'extrait méthanolique d'Angelica sinensis était le plus efficace pour réduire la néphrotoxicité induite par le cisplatine. Ces principes actifs – l'acide férulique, le Z-ligustilide et le E-ligustilide – ont été testés selon la même méthodologie. <p>L'acide férulique a été le plus efficace pour améliorer la survie cellulaire et diminuer l'apoptose induite par le cisplatine. Il a également permis de réduire la production de matrice extracellulaire, de stimuler les capacités de régénération de cellules saines et d'inhiber partiellement la voie de signalisation de la β-caténine. Il n'a toutefois pas été capable de limiter la génération de stress oxydatif induite par le traitement au cisplatine. <p>L'acide férulique semble être un candidat prometteur pour protéger les tubules rénaux vis-à-vis du cisplatine et pourrait contribuer à limiter l'initiation et le développement de la fibrose rénale. <p>/<p>The kidneys are targets of numerous toxic compounds. Proximal tubular epithelia cells are particularly vulnerable to xenobiotics used as drugs or not. These injuries can be associated with an increased oxidative stress and can trigger cell death. They can also lead to the loss of phenotypic characteristics of epithelial cells and initiate their dedifferentiation in mesenchymal cells, eventually evolving in fibroblasts, major actors responsible for renal fibrosis. <p>Protective strategies – including those implemented in clinical practice during the administration of nephrotoxic drugs – relying on a pharmacological approach remain seldom.<p>By means of data issuing from traditional medicines, we selected a series of herbs potentially useful for the treatment or prevention of troubles associated with kidney diseases: Angelicae sinensis radix, Eleutherococci radix, Ginseng radix, Schisandrae chinensis fructus and Silybi mariani fructus.<p>Using an in vitro model based on HK-2 cell line, we examined if these herbal products could bring an effective protection towards 3 nephrotoxic drugs: aristolochic acids, cisplatin and ciclosporin. Five phenomena involved in nephrotoxicity and regularly occurring during the progression of renal fibrosis were investigated: (i) cell death and apoptosis; (ii) oxidative stress generation; (iii) modulation of regeneration capacities; (iv) extracellular matrix production; and (v) β-catenin pathway activation.<p>Among the 5 herbs that were studied, the one presenting the most interesting effects towards one of the 3 toxicants has been investigated in details in order to identify the compound(s) responsible for its bioactivity. Results indicated that the crude methanolic extract of Angelica sinensis was the most potent for reducing cisplatin-induced nephrotoxicity. Its active principles – ferulic acid, Z-ligustilide and E-ligustilide – were tested according to the same methods.<p>Ferulic acid was the most potent compound for improving cell survival and for alleviating cisplatine-induced apoptosis. It also allowed to restrain the extracellular matrix production, enhanced the regeneration capacities of healthy cells and partially inhibited the activation of the β-catenin pathway. It was however ineffective in preventing the generation of oxidative stress induced during cisplatin treatment. <p>Ferulic acid appears as a promising candidate for protecting renal tubules against cisplatin's nephrotoxicity and could contribute to limit the onset and progression of renal fibrosis.<br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished

Anaerobic ammonium oxidation (anammox) by anammox bacteria contributes significantly to the global nitrogen cycle and plays a major role in sustainable wastewater treatment. To date, autotrophic nitrogen removal by anammox bacteria is the most efficient and environmentally friendly process for the treatment of ammonium in wastewaters; its application can save up to 60% of the energy input, nearly 100% elimination of carbon demand and 80% decrease in excess sludge compared to conventional nitrification/denitrification process. In the anammox process, ammonium (NH4+) is directly oxidized to dinitrogen gas (N2) using intracellular electron acceptors such as nitrite (NO2–) or nitric oxide (NO). In the absence of NO2– or NO, anammox bacteria can couple formate oxidation to the reduction of metal oxides such as Fe(III) or Mn(IV). Their genomes contain homologs of Geobacter and Shewanella cytochromes involved in extracellular electron transfer (EET). However, it is still unknown whether anammox bacteria have EET capability and can couple the oxidation of NH4+ with transfer of electrons to extracellular electron acceptors. In this dissertation, I discovered by using complementary approaches that in the absence of NO2–, freshwater and marine anammox bacteria couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). Metagenomics, fluorescence in-situ hybridization and electrochemical analyses coupled with MEC performance confirmed that anammox electrode biofilms were responsible for current generation through EET-dependent oxidation of NH4+. 15N-labelling experiments revealed the molecular mechanism of the EET-dependent anammox process. NH4+ was oxidized to N2 via hydroxylamine (NH2OH) as intermediate when electrode was used as the terminal electron acceptor. Comparative transcriptomics analysis supported isotope labelling experiments and revealed an alternative pathway for NH4+ oxidation coupled to EET when electrode was used as electron acceptor. The results presented in my dissertation provide the first experimental evidence that marine and freshwater anammox bacteria can couple NH4+ oxidation with EET, which is a significant breakthrough that is promising in the context of implementing EET-dependent anammox process for energy-efficient treatment of nitrogen using bioelectrochemical systems.

The aerobic oxidation of organic material by microbes is the focus of this chapter. Microbes account for about 50% of primary production in the biosphere, but they probably account for more than 50% of organic material oxidization and respiration (oxygen use). The traditional role of microbes is to degrade organic material and to release plant nutrients such as phosphate and ammonium as well as carbon dioxide. Microbes are responsible for more than half of soil respiration, while size fractionation experiments show that bacteria are also responsible for about half of respiration in aquatic habitats. In soils, both fungi and bacteria are important, with relative abundances and activity varying with soil type. In contrast, fungi are not common in the oceans and lakes, where they are out-competed by bacteria with their small cell size. Dead organic material, detritus, used by microbes, comes from dead plants and waste products from herbivores. It and associated microbes can be eaten by many eukaryotic organisms, forming a detritus food web. These large organisms also break up detritus into small pieces, creating more surface area on which microbes can act. Microbes in turn need to use extracellular enzymes to hydrolyze large molecular weight compounds, which releases small compounds that can be transported into cells. Fungi and bacteria use a different mechanism, “oxidative decomposition,” to degrade lignin. Organic compounds that are otherwise easily degraded (“labile”) may resist decomposition if absorbed to surfaces or surrounded by refractory organic material. Addition of labile compounds can stimulate or “prime” the degradation of other organic material. Microbes also produce organic compounds, some eventually resisting degradation for thousands of years, and contributing substantially to soil organic material in terrestrial environments and dissolved organic material in aquatic ones. The relationship between community diversity and a biochemical process depends on the metabolic redundancy among members of the microbial community. This redundancy may provide “ecological insurance” and ensure the continuation of key biogeochemical processes when environmental conditions change.

Diabetic kidney disease (DKD) is the most common cause of ESRD in USA as well as in the world. The incidence and the prevalence of DKD have been increasing regardless of current intervention. The pathology of DKD is characterized by accumulation of extracellular matrix in GBM and mesangial area. The pathogenesis of DKD is multi-factorial including genetic, metabolic, and hemodynamic changes, which lead to activation of oxidative stress, inflammation, and fibrosis pathways in the diabetic kidney. Clinically, patients with DKD presents with glomerular hyperfiltration at early stage, then microalbuminuria, macroalbuminuria, and ESRD. However, the disease progression varies greatly among individual patients. Treatment of DKD is limited to hyperglycemic and blood pressure control and use of RAS blockade. Several new drugs such as SGLT2 inhibitors have been on phase 3 clinical trials but research is required to develop more effective drugs to treat DKD.

Type 2 diabetes mellitus (T2DM) is a widely spread metabolic disease, the initial stages of which are asymptomatic and have no clinically recognizable manifestation. At the molecular level, T2DM is manifested with essential non-enzymatic structural changes of intra- and extracellular proteins, mostly represented with oxidation and glycation of multiple residues. Protein glycation is one of the most universal markers of T2DM, and is recognized as an indirect, but adequate indicator of plasma glucose levels over prolonged periods of time. Unfortunately, glycated hemoglobin (HbA1c) – the universally accepted T2DM marker, is insensitive for short-term excursions of blood glucose, which are known to precede the onset of disease. Therefore, new generation biomarkers, giving access to the time dimension of Maillard reaction in blood, are desired. In this context, establishment of individual glycation sites of plasma proteins as new T2DM biomarkers might be a promising approach. Indeed, involvement of proteins with different half-life times in such analysis will make the time dimension of protein glycation in blood available and will allow early recognition of blood sugar fluctuations, occurring within few weeks or even days.