Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to evaluate the effects of metal ions, which may be released from orthopedic or dental implants, on osteoblast metabolism and differentiation. ROS 17/2.8 cells were cultured in F-12 medium for 7 days. Then Al+3, Co+2, Cr+3, Ni+2, Ti+4, and V+3 were added at concentrations less than their cytotoxic concentrations. After 3 days, DNA synthesis, succinate dehydrogenase activity, alkaline phosphatase (ALP) activity, and culture calcification were assessed. Northern blots were performed for ALP, osteocalcin (OCN), and osteopontin (OPN) mRNA transcription. The data indicated that Cr+3 and A1+3 had few inhibitory effects on ROS cell metabolism below their cytotoxic concentrations, Ni+2, Co+2, Ti+4, and V+3 affected all these parameters of ROS cell metabolism at concentrations below cytotoxic levels. For RNA analysis, A1+3 significantly suppressed the expression of ALP, OCN, and OPN at both cytotoxic and noncytoxic concentrations. Co+2 specifically suppressed ALP expression at cytotoxic concentrations. Cr+3 and Ni+2 inhibited OCN, OPN, and ALP gene expression only at cytotoxic concentrations. For Ti+4 and V+3 ions, gene expression at cytotoxic levels was not significantly affected as compared with the effects at noncytotoxic level. These results show that metal ions may alter osteoblast behavior even at subtoxic concentrations, but do not always affect the expression of all genes similarly.
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PMID:Effects of metal ions on osteoblast-like cell metabolism and differentiation. 897 50

Prolonged use of contact lenses (for 14 days) evoked an imbalance between the activity of xanthine oxidase (an enzyme belonging to reactive oxygen species-generating oxidases) and catalase (an enzyme belonging to reactive oxygen species-scavenging oxidases) in the corneal epithelium of rabbits. The activity of catalase decreased, while xanthine oxidase activity was very high. Of other enzymes studied in the corneal epithelium, the activities of xanthine oxidoreductase, glucoso-6-phosphate dehydrogenase and succinate dehydrogenase were decreased. In contrast, the activities of lactate dehydrogenase and lysosomal hydrolases (acid beta-galactosidase, dipeptidyl peptidase II) were increased and appeared in animals sacrificed immediately after contact lens removal. In rabbits sacrificed later (after 1 h), an additional increase of lactate dehydrogenase and lysosomal hydrolase activities developed in the superficial layers of the corneal epithelium. Catalase supplementation during use of contact lenses prevented both the significant decrease of catalase activity in the corneal epithelium and the development of additional epithelial damage. In contrast, topical treatment with 3-aminotriazole (an inhibitor of catalase) resulted in the nearly complete loss of catalase activity in the corneal epithelium and the appearance of more serious epithelial damage. We conclude that ROS generated by xanthine oxidase induce additional damage of the corneal epithelium related to the use of contact lenses.
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PMID:Reactive oxygen species (ROS) generated by xanthine oxidase in the corneal epithelium and their potential participation in the damage of the corneal epithelium after prolonged use of contact lenses in rabbits. 958 28

Oxygen free radicals (ROS) of mitochondrial origin seem to be involved in aging. Whereas in other tissues complexes I or III of the respiratory chain contain the ROS generators, in this study we find that rat liver mitochondria generate oxygen radicals at complexes I, II, and III. Short-term (6 weeks) caloric restriction significantly decreased H2O2 production in rat liver mitochondria. This decrease in ROS production was located at complex I because it occurred with complex I-linked substrates (pyruvate/malate), but did not reach statistical significance with the complex II-linked substrate succinate. The mechanism responsible for the lowered ROS production was not a decrease in oxygen consumption. Instead, the mitochondria of caloric-restricted animals released less ROS per unit electron flow. This was due to a decrease in the degree of reduction of the complex I generator. Furthermore, oxidative damage to mitochondrial and nuclear DNA was also decreased in the liver by short-term caloric restriction. The results agree with the idea that caloric restriction delays aging, at least in part, by decreasing the rate of mitochondrial ROS generation and thus the rate of attack to molecules, like DNA, highly relevant for the accumulation of age-dependent changes.
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PMID:Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source. 1171 Aug 4

The effect of long-term caloric restriction and aging on the rates of mitochondrial H2O2 production and oxygen consumption as well as on oxidative damage to nuclear (nDNA) and mitochondrial DNA (mtDNA) was studied in rat liver tissue. Long-term caloric restriction significantly decreased H2O2 production of rat liver mitochondria (47% reduction) and significantly reduced oxidative damage to mtDNA (46% reduction) with no changes in nDNA. The decrease in ROS production was located at complex I because it only took place with complex I-linked substrates (pyruvate/malate) but not with complex II-linked substrates (succinate). The mechanism responsible for that decrease in ROS production was not a decrease in mitochondrial oxygen consumption because it did not change after long-term restriction. Instead, the caloric restricted mitochondria released less ROS per unit electron flow, due to a decrease in the reduction degree of the complex I generator. On the other hand, increased ROS production with aging in state 3 was observed in succinate-supplemented mitochondria because old control animals were unable to suppress H2O2 production during the energy transition from state 4 to state 3. The levels of 8-oxodG in mtDNA increased with age in old animals and this increase was abolished by caloric restriction. These results support the idea that caloric restriction reduces the aging rate at least in part by decreasing the rate of mitochondrial ROS production and so, the rate of oxidative attack to biological macromolecules like mtDNA.
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PMID:Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria. 1197 89

Hypoxia induces an increase in the ROS generation by cells of small intrapulmonary vessels. Based on our results we suppose that this is caused by a switch in the catalytic activity of mitochondrial complex II from succinate dehydrogenase to fumarate reductase. Functional complex II is also necessary for hypoxic pulmonary vasoconstriction.
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PMID:Mitochondrial complex II is essential for hypoxia-induced ROS generation and vasoconstriction in the pulmonary vasculature. 1463 63

1. One hundred and sixty 1-d-old Arbor Acre male broiler chicks were fed with maize-soybean based diets for 6 weeks in a 2 x 2 factorial experiment. The factors were CoQ10 supplementation (0 or 40 mg/kg) and Escherichia coli lipopolysaccharide (LPS) challenge (LPS or saline). 2. CoQ10 was supplemented from d 1. From d 18, the chickens received three weekly i.p. injections of LPS (1.0 mg/kg BW) or an equivalent amount of sterile saline as control. From d 10 on, all chickens were exposed to low ambient temperature (12 to 15 degrees C) to induce ascites. 3. The blood packed cell volume and ascites heart index of broiler chickens were reduced by dietary CoQ10 supplementation. Mitochondrial State 3 and State 4 respiration, respiratory control ratio and phosphate oxygen ratio were not changed, but H+/site stoichiometry of complex II + III was elevated by dietary CoQ10 supplementation. 4. Cytochrome c oxidase and H+-ATPase activity were increased by CoQ10 supplementation, whereas NADH cytochrome c reductase and succinate cytochrome c reductase were not influenced. Mitochondrial anti-ROS capability was increased and malondialdehyde content was decreased by CoQ10 supplementation. 5. The work suggested that dietary CoQ10 supplementation could reduce broiler chickens' susceptibility to ascites, which might be the result of improving hepatic mitochondrial function, some respiratory chain-related enzymes activities and mitochondrial antioxidative capability.
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PMID:Effects of dietary coenzyme Q10 supplementation on hepatic mitochondrial function and the activities of respiratory chain-related enzymes in ascitic broiler chickens. 1635 19

Many previous investigations have consistently reported that caloric restriction (40%), which increases maximum longevity, decreases mitochondrial reactive species (ROS) generation and oxidative damage to mitochondrial DNA (mtDNA) in laboratory rodents. These decreases take place in rat liver after only seven weeks of caloric restriction. Moreover, it has been found that seven weeks of 40% protein restriction, independently of caloric restriction, also decrease these two parameters, whereas they are not changed after seven weeks of 40% lipid restriction. This is interesting since it is known that protein restriction can extend longevity in rodents, whereas lipid restriction does not have such effect. However, before concluding that the ameliorating effects of caloric restriction on mitochondrial oxidative stress are due to restriction in protein intake, studies on the third energetic component of the diet, carbohydrates, are needed. In the present study, using semipurified diets, the carbohydrate ingestion of male Wistar rats was decreased by 40% below controls without changing the level of intake of the other dietary components. After seven weeks of treatment the liver mitochondria of the carbohydrate restricted animals did not show changes in the rate of mitochondrial ROS production, mitochondrial oxygen consumption or percent free radical leak with any substrate (complex I- or complex II-linked) studied. In agreement with this, the levels of oxidative damage in hepatic mtDNA and nuclear DNA were not modified in carbohydrate restricted animals. Oxidative damage in mtDNA was one order of magnitude higher than that in nuclear DNA in both dietary groups. These results, together with previous ones, discard lipids and carbohydrates, and indicate that the lowered ingestion of dietary proteins is responsible for the decrease in mitochondrial ROS production and oxidative damage in mtDNA that occurs during caloric restriction.
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PMID:Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage. 1713 10

In the perinatal period, adrenomedullary chromaffin cells (AMC) directly sense PO2 and secrete catecholamines during hypoxic stress, and this response is lost in juvenile ( approximately 2 week-old) chromaffin cells following postnatal innervation. Here we tested the hypothesis that a rotenone-sensitive O2-sensor and ROS are involved in the hypoxic response of AMC cultured from neonatal and juvenile rats. In whole-cell recordings, hypoxia (PO2=5-15 mm Hg) inhibited outward current in neonatal AMC; this response was reversed by exogenous H2O2 and mimicked and occluded by intracellular catalase (1000 units/ml), as well as the antioxidants, N-acetyl-L-cysteine (NAC; 50 microM) and Trolox (200 microM). Acute hypoxia decreased ROS levels and stimulated ATP secretion in these cells, as measured by luminol and luciferin-luciferase chemiluminescence, respectively. Of several mitochondrial electron transport chain (ETC) inhibitors tested, only rotenone, a complex I blocker, mimicked and occluded the effects of hypoxia on outward current, cellular ROS, and ATP secretion. Succinate donors, which act as complex II substrates, reversed the effects of hypoxia and rotenone in neonatal AMC. In contrast, in hypoxia-insensitive juvenile AMC, neither NAC nor rotenone stimulated ATP secretion though they both caused a decrease in ROS levels. We propose that O2-sensing by neonatal AMC is mediated by decreased ROS generation via a rotenone-sensitive site that is coupled to outward current inhibition and secretion. Interestingly, juvenile AMC display at least two modifications, i.e. an uncoupling of the O2-sensor from ROS regulation, and an apparent insensitivity of outward current to decreased ROS.
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PMID:A rotenone-sensitive site and H2O2 are key components of hypoxia-sensing in neonatal rat adrenomedullary chromaffin cells. 1720 76

Nuclear respiratory factor-1 (NRF-1) is integral to the transcriptional regulation of mitochondrial biogenesis, but its control over various respiratory genes overlaps other regulatory elements including those involved in O(2) sensing. Aerobic metabolism generally suppresses hypoxia-sensitive genes, e.g. via hypoxia-inducible factor-1 (HIF-1), but mutations in Complex II-succinate dehydrogenase (SDH), a tumor suppressor, stabilize HIF-1, producing pseudo-hypoxia. In aerobic cardiomyocytes, which rely on oxidative phosphorylation, we tested the hypothesis that NRF-1 regulates Complex II expression and opposes hypoxia-inducible factor-1. NRF-1 gene silencing blocked aerobic succinate oxidation, increasing nuclear HIF-1alpha protein prior to the loss of Complex I function. We postulated that NRF-1 suppression either specifically decreases the expression of one or more SDH subunits and increases succinate availability to regulate HIF-1 prolyl hydroxylases, or stimulates mitochondrial reactive oxygen production, which interferes with HIF-1alpha degradation. Using promoter analysis, gene silencing, and chromatin immunoprecipitation, NRF-1 was found to bind to the gene promoters of two of four nuclear-encoded Complex II subunits: SDHa and SDHd, but the enzyme activity was dynamically regulated through the catalytic SDHa flavoprotein. Complex II was inactivated by SDHa silencing, which led to aerobic HIF-1alpha stabilization, nuclear translocation, and enhanced expression of glucose transporters and heme oxygenase-1. This was unrelated to mitochondrial ROS production, reversible by high alpha-ketoglutarate concentrations, and coherent with regulation of HIF-1 by succinate reported in tumor cells. These findings disclose a novel role for NRF-1 in the transcriptional control of Complex II and prevention of pseudo-hypoxic gene expression in aerobic cardiac cells.
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PMID:Transcriptional Regulation of SDHa flavoprotein by nuclear respiratory factor-1 prevents pseudo-hypoxia in aerobic cardiac cells. 1825 25

The purpose of this study was to determine the effects and mechanisms of sCD40L on endothelial dysfunction in both human coronary artery endothelial cells (HCAECs) and porcine coronary artery rings. HCAECs treated with sCD40L showed significant reductions of endothelial nitric oxide synthase (eNOS) mRNA and protein levels, eNOS mRNA stability, eNOS enzyme activity, and cellular NO levels, whereas superoxide anion (O(2)(-)) production was significantly increased. sCD40L enhanced eNOS mRNA 3'UTR binding to cytoplasmic molecules and induced a unique expression pattern of 95 microRNAs. sCD40L significantly decreased mitochondrial membrane potential, and catalase and SOD activities, whereas it increased NADPH oxidase (NOX) activity. sCD40L increased phosphorylation of MAPKs p38 and ERK1/2 as well as IkappaBalpha and enhanced NF-kappaB nuclear translocation. In porcine coronary arteries, sCD40L significantly decreased endothelium-dependent vasorelaxation and eNOS mRNA levels, whereas it increased O(2)(-) levels. Antioxidant seleno-l-methionine; chemical inhibitors of p38, ERK1/2, and mitochondrial complex II; as well as dominant negative mutant forms of IkappaBalpha and NOX4 effectively blocked sCD40L-induced eNOS down-regulation in HCAECs. Thus, sCD40L reduces eNOS levels, whereas it increases oxidative stress through the unique molecular mechanisms involving eNOS mRNA stability, 3'UTR-binding molecules, microRNAs, mitochondrial function, ROS-related enzymes, p38, ERK1/2, and NF-kappaB signal pathways in endothelial cells.
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PMID:Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells. 1865 29


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