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:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of our study was to investigate the effect of a single high intensity session of muscle contractions on the activity and expression of citrate synthase (CS) and of the following major antioxidant enzymes: Mn-superoxide dismutase (Mn-SOD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT), and glutathione peroxidase (GPX). To accomplish this, soleus muscles of male Wistar rats were subjected to contractions using a intense electrical stimulation (ES) protocol. Soleus muscles were isolated either immediately or 1 h after the contractions and utilized for enzyme activity determination, and for analysis of gene expression by quantitative PCR. A significant increase in maximal activity (63%) and expression (80%) of CS was observed in stimulated soleus muscles, isolated 1 h after ES as compared to controls. However, this effect was not observed in muscles isolated immediately after ES. By using macroarray and Real Time RT-PCR analysis, an increase in expression of Mn-SOD, Cu,Zn-SOD, CAT, and GPX was also found. Interestingly, of these enzymes, only CAT activity was significantly increased (44%) 1 h after ES in soleus muscle. These results indicate that acute ES up-regulates activity and expression of CS and CAT in soleus muscles. This increase in expression of CAT may play an important role in counteracting the potential deleterious effects of elevated oxidative stress induced by a high oxidative demand in skeletal muscles subjected to exercise training.
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PMID:Effect of a single session of electrical stimulation on activity and expression of citrate synthase and antioxidant enzymes in rat soleus muscle. 1796 76

Amitriptyline is a tricyclic antidepressant widely used in the treatment of chronic pain. The objective of the present study was to investigate the potential cytotoxic effects of amitriptyline in human fibroblasts primary culture. Human fibroblast cells were cultured from healthy subjects and incubated with 50 microM and 100 microM amitriptyline. Cell counting was performed to study dose-dependency of toxicity. Lipid peroxidation analysis and western blotting for antioxidants catalase and mitochondrial superoxide dismutase (MnSOD) were carried out in order to evaluate oxidative stress. To investigate mitochondria damage the following determinations were made: cytochrome c, citrate synthase, and mitochondrial membrane potential (DeltaPsi(m)). Amitriptyline reduced significantly the number of cultured cells, resulting in a decrease of 45.2%, 65.0% and 94.9% when treated with 20 microM, 50 microM and 100 microM amitriptyline, respectively. This drug enhanced the production of oxidized products during lipid peroxidation, inverting the reduced/oxidized ratio to 25% reduction and 75% oxidation after 24h of amitriptyline administration. A decreased in catalase protein levels has been also observed. Moreover, amitriptyline treatment induced a significant decrease of cytochrome c, DeltaPsi(m), and citrate synthase activity; revealing mitochondrial damage. These findings suggest that amitriptyline has a strong cytotoxic effect in human fibroblasts, decreasing growth rate and mitochondrial activity, and increasing oxidative stress.
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PMID:Cytotoxic effects of amitriptyline in human fibroblasts. 1798 Apr 74

Dendritic cells (DC) are potent antigen-presenting cells capable of inducing T and B responses and immune tolerance. We have characterized some aspects of energy metabolism accompanying the differentiation process of human monocytes into DC. Compared to precursor monocytes, DC exhibited a much larger number of mitochondria and consistently (i) a higher endogenous respiratory activity and (ii) a more than sixfold increase in ATP content and an even larger increase in the activity of the mitochondrial marker enzyme citrate synthase. The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability. Rotenone inhibited DC differentiation, as revealed by the observation that the expression of CD1a, which is a specific surface marker of DC differentiation, was strongly reduced. Cells cultured in the presence of rotenone displayed a lower content of growth factor-induced, mitochondrially generated, hydrogen peroxide. A similar drop in ROS was observed upon addition of catalase, which caused functional effects similar to those produced by rotenone treatment. These results suggest that ROS play a crucial role in DC differentiation and that mitochondria are an important source of ROS in this process.
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PMID:Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions. 1824 95

To date, the only reported metabolic and physiological roles for carnitine in Saccharomyces cerevisiae are related to the activity of the carnitine shuttle. In yeast, the shuttle transfers peroxisomal activated acetyl-residues to the mitochondria. However, acetyl-CoA can also be metabolised by the glyoxylate cycle to form succinate. The two pathways, therefore, provide a metabolic bypass for each other, and carnitine-dependent phenotypes have only been described in strains with non-functional peroxisomal citrate synthase, Cit2p. Here, we present evidence for a role of carnitine in stress protection that is independent of CIT2 and of the carnitine shuttle. Data show that carnitine improves growth during oxidative stress and in the presence of weak organic acids in wt and in CAT deletion strains. Our data also show that strains with single, double and triple deletions of the three CAT genes generally present identical phenotypes, but that the deletion of CAT2 decreases survival during oxidative stress in a carnitine-independent manner. Overexpression of single CAT genes does not lead to cross-complementation, suggesting a highly specific metabolic role for each enzyme. The data suggest that carnitine protects cells from oxidative and organic acid stress, while CAT2 contributes to the response to oxidative stress.
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PMID:Carnitine and carnitine acetyltransferases in the yeast Saccharomyces cerevisiae: a role for carnitine in stress protection. 1842 9

The ocean quahog Arctica islandica is the longest-lived of all bivalve and molluscan species on earth. Animals close to 400 years are common and reported maximum live span around Iceland is close to 400 years. High and stable antioxidant capacities are a possible strategy to slow senescence and extend lifespan and this study has investigated several antioxidant parameters and a mitochondrial marker enzyme in a lifetime range spanning from 4-200 years in the Iceland quahog. In gill and mantle tissues of 4-192 year old A. islandica, catalase, citrate synthase activity and glutathione concentration declined rapidly within the first 25 years, covering the transitional phase of rapid somatic growth and sexual maturation to the outgrown mature stages (approximately 32 years). Thereafter all three parameters kept rather stable levels for > 150 years. In contrast, superoxide dismutase activities maintained high levels throughout life time. These findings support the 'Free Radical-Rate of Living theory', antioxidant capacities of A. islandica are extraordinarily high and thus may explain the species long life span.
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PMID:Imperceptible senescence: ageing in the ocean quahog Arctica islandica. 1848 11

The aim of this study was to investigate the effect of different protocols of physical exercise on oxidative stress markers in mouse liver. Twenty-eight male CF1 mice (30-35 g) were distributed into 4 groups (n = 7) - untrained (UT), continuous running (CR), downhill running (D-HR), and intermittent running (IR) - and underwent an 8-week training program. Forty-eight hours after the last training session, the animals were killed, and their livers were removed. Blood lactate, creatine kinase, citrate synthase, thiobarbituric acid reactive species, carbonyl, superoxide dismutase (SOD), and catalase (CAT) activities were assayed. Results show a decrease in the level of lipoperoxidation and protein carbonylation in the CR and D-HR groups. SOD activity was significantly increased and CAT activity was reduced in the CR and D-HR groups. Our findings indicate that CR and D-HR may be important for decreasing oxidative damage and in the regulation of antioxidant enzymes (SOD and CAT) in the livers of trained mice.
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PMID:Effect of different models of physical exercise on oxidative stress markers in mouse liver. 1923 86

Fatty liver has been linked to low aerobic fitness, but the mechanisms are unknown. We previously reported a novel model in which rats were artificially selected to be high capacity runners (HCR) and low capacity runners (LCR) that in a sedentary condition have robustly different intrinsic aerobic capacities. We utilized sedentary HCR/LCR rats (generation 17; max running distance equalled 1514 +/- 91 vs. 200 +/- 12 m for HCR and LCR, respectively) to investigate if low aerobic capacity is associated with reduced hepatic mitochondrial oxidative capacity and increased susceptibility to hepatic steatosis. At 25 weeks of age, LCR livers displayed reduced mitochondrial content (reduced citrate synthase activity and cytochrome c protein) and reduced oxidative capacity (complete palmitate oxidation in hepatic mitochondria (1.15 +/- 0.13 vs. 2.48 +/- 1.1 nm g(-1) h, P < 0.0001) and increased peroxisomal activity (acyl CoA oxidase and catalase activity) compared to the HCR. The LCR livers also displayed a lipogenic phenotype with higher protein content of both sterol regulatory element binding protein-1c and acetyl CoA carboxylase. These differences were associated with hepatic steatosis in the LCR including higher liver triglycerides (6.00 +/- 0.71 vs. 4.20 +/- 0.39 nmol g(-1), P = 0.020 value), >2-fold higher percentage of hepatocytes associated with lipid droplets (54.0 +/- 9.2 vs. 22.0 +/- 3.5%, P = 0.006), and increased hepatic lipid peroxidation compared to the HCR. Additionally, in rats aged to natural death, LCR livers had significantly greater hepatic injury (fibrosis and apoptosis). We provide novel evidence that selection for low intrinsic aerobic capacity causes reduced hepatic mitochondrial oxidative capacity that increases susceptibility to both hepatic steatosis and liver injury.
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PMID:Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury. 1936 5

Emerging evidence indicates that impaired mitochondrial fatty acid beta-oxidation plays a key role in liver steatosis. We have recently demonstrated that increased angiotensin (ANG) II causes progressive hepatic steatosis associated with oxidative stress; however, the underlying mechanisms remain unclear. We hypothesized that ANG II causes hepatic mitochondrial oxidative damage and impairs mitochondrial beta-oxidation, thereby leading to hepatic steatosis. We used the Ren2 rat with elevated endogenous ANG II levels to evaluate mitochondrial ultrastructural changes, gene expression levels, and beta-oxidation. Compared with Sprague-Dawley littermates, Ren2 livers exhibited mitochondrial damage and reduced beta-oxidation, as evidenced by ultrastructural abnormalities, decrease of mitochondrial content, percentage of palmitate oxidation to CO(2), enzymatic activities (beta-HAD and citrate synthase), and the expression levels of cytochrome c, cytochrome c oxidase subunit 1, and mitochondrial transcription factor A. These abnormalities were improved with either ANG II receptor blocker valsartan or superoxide dismutase/catalase mimetic tempol treatment. Both valsartan and tempol substantially attenuated mitochondrial lipid peroxidation in Ren2 livers. Interestingly, there was no difference in the expression of key enzymes (ACC1 and FAS) for fatty acid syntheses and their transcription factors (SREBP-1c and ChREBP) between Sprague-Dawley, untreated Ren2, and valsartan- or tempol-treated Ren2 rats. These results document that ANG II induces mitochondrial oxidative damage and impairs mitochondrial beta-oxidation, contributing to liver steatosis.
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PMID:Oxidative stress-mediated mitochondrial dysfunction contributes to angiotensin II-induced nonalcoholic fatty liver disease in transgenic Ren2 rats. 1996 4

Acute exercise in mice induces intestinal lymphocyte (IL) apoptosis. Freewheel running reduces apoptosis and forced exercise training increases splenocyte antioxidant levels. The purpose of this study was to examine the effect of freewheel running and acute exercise on mouse IL numbers and concentrations of apoptosis and antioxidant proteins and pro-inflammatory cytokines in IL. Female C57BL/6 mice had access to in-cage running wheels (RW) or cages without wheels (NRW) for 16 weeks and were randomized at the end of training to no exercise control (TC) or to treadmill exercise with sacrifice after 90 min of running (TREAD; 30 min, 22 m min(-1); 30 min, 25 m min(-1); 30 min, 28 m min(-1); 2 degrees slope). IL were analyzed for pro-(caspase 3 and 7) and anti-(Bcl-2) apoptotic proteins, endogenous antioxidants (glutathione peroxidase: GPx; catalase: CAT) and the pro-inflammatory cytokine, TNF-alpha. RW mice had higher cytochrome oxidase (p<0.001) and citrate synthase (p<0.01) activities in plantaris and soleus muscles and higher GPx and CAT expression in IL (p<0.05) (indicative of training) compared with NRW mice. TNF-alpha expression was lower (p<0.05) and IL numbers higher (p<0.05) in RW vs. NRW mice. No training effect was observed for apoptotic protein expression, although TREAD resulted in higher caspase and lower Bcl-2. These results suggest that freewheel running in mice for 16 weeks enhances antioxidant and reduces TNF-alpha expression in IL but does not reduce pro-apoptotic protein expression after acute exercise. Results are discussed in terms of implications for inflammatory bowel diseases where apoptotic proteins and TNF-alpha levels are elevated.
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PMID:Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-alpha in intestinal lymphocytes. 1948 47

Cold acclimation of ectotherms results typically in enhanced oxidative capacities and lipid remodeling, changes that should increase the risk of lipid peroxidation (LPO). It is unclear whether activities of antioxidant enzymes may respond in a manner to mitigate the increased potential for LPO. The current study addresses these questions using killifish (Fundulus heteroclitus macrolepidotus) and bluegill (Lepomis macrochirus) acclimated to 5 and 25 degrees C for 9 days and 2 months, respectively. Because the effects of temperature acclimation on pro- and antioxidant metabolism may be confounded by variable activity levels among temperature groups, one species (killifish) was also subjected to a 9-day exercise acclimation. Oxidative capacity of glycolytic (skeletal) muscle (indicated by the activity of cytochrome c oxidase) was elevated by 1.5-fold in killifish, following cold acclimation, but was unchanged in cardiac muscle and also unaffected by exercise acclimation in either tissue. No changes in citrate synthase activity were detected in either tissue following temperature acclimation. Enzymatic antioxidants (catalase and superoxide dismutase) of either muscle type were unaltered by temperature or exercise acclimation. Mitochondria from glycolytic muscle of cold-acclimated killifish were enriched in highly oxidizable polyunsaturated fatty acids (PUFA), including diacyl phospholipids (total carbons:total double bonds) 40:8 and 44:12. Increased oxidative capacity, coupled with elevated PUFA content in mitochondria from cold-acclimated animals did not, however, impact LPO susceptibility when measured with C11-BODIPY. The apparent mismatch between oxidative capacity and enzymatic antioxidants following temperature acclimation will be addressed in future studies.
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PMID:Temperature acclimation alters oxidative capacities and composition of membrane lipids without influencing activities of enzymatic antioxidants or susceptibility to lipid peroxidation in fish muscle. 2008 29


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