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:1.1.1.41 (isocitrate dehydrogenase)
3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generation of reactive oxygen species and mitochondrial dysfunction has been implicated in adriamycin induced cardiotoxicity. Mitochondrial dysfunction is characterized by the accumulation of oxidized lipids, proteins and DNA, leading to disorganization of mitochondrial structure and systolic failure. The present study was aimed to evaluate the efficacy of Centella asiatica on the mitochondrial enzymes; mitochondrial antioxidant status in adriamycin induced myocardial injury. Adriamycin (2.5 mg/kg body wt., i.p.) induced mitochondrial damage in rats was assessed in terms of decreased activities (p<0.05) of cardiac marker enzymes (lactate dehydrogenase, creatine phosphokinase, amino transferases), TCA cycle enzymes (isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase, respiratory marker enzymes (NADH-dehydrogenase, cytochrome-C-oxidase), mitochondrial antioxidant enzymes (GPx, GSH, SOD,CAT) and increased (p<0.05) level of lipid peroxidation. Mitochondrial damage was confirmed by transmission electron microscopic examination. Pre-co-treatment with aqueous extract of Centella asiatica (200 mg/kg body wt, oral) effectively counteracted the alterations in mitochondrial enzymes and mitochondrial defense system. In addition, transmission electron microscopy study confirms the restoration of cellular normalcy and accredits the cytoprotective role of Centella asiatica against adriamycin induced myocardial injury. Our results demonstrated elevated oxidative stress and mitochondrial dysfunction in adriamycin treated rats. Moreover, on the basis of our findings it may be concluded that the aqueous extract of C. asiatica not only possesses antioxidant properties but it may also reduce the extent of mitochondrial damage.
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PMID:Adriamycin induced myocardial failure in rats: protective role of Centella asiatica. 1678 85

The neuroprotective effect of mitochondrial isocitrate dehydrogenase (IDPm), an enzyme involved in the reduction of NADP(+) to NADPH and the supply of glutathione (GSH) in mitochondria, was examined using SH-SY5Y cells overexpressing IDPm (S1). S1 cells showed higher NADPH and GSH levels than vector transfectant (V) cells and were more resistant to staurosporine-induced cell death than controls. Staurosporine-induced cytochrome c release, caspase-3 activation, and production of reactive oxygen species (ROS) were significantly attenuated in S1 cells as compared to V cells and reduced by antioxidants, trolox and GSH-ethyl ester (GSH-EE). Staurosporine-induced the release of Mcl-1 from mitochondria that formed a complex with Bim. Mcl-1 was then cleaved to a shortened form in a caspase-3 dependent manner; its release was attenuated far more in S1 than in V cells after staurosporine treatment. Finally, the staurosporine-induced decrease in mitochondrial membrane potential (Deltapsi(m)) was correlated with the time of mitochondrial Mcl-1 release; the loss of Deltapsi(m) was attenuated significantly in S1 cells as compared to that in V cells. These results suggest that the neuroprotective effect of IDPm may result from increases in NADPH and GSH levels in the mitochondria. This, in turn, inhibits mitochondrial ROS production after cytochrome c release, which seems to be mediated through Mcl-1 release.
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PMID:Mitochondrial isocitrate dehydrogenase protects human neuroblastoma SH-SY5Y cells against oxidative stress. 1707 1

Peroxynitrite, a potent physiological inorganic toxin, is known to play a critical role in cellular oxidative damage. The protective role of antioxidant enzymes against peroxynitrite-induced oxidative damage in U937 cells was investigated in control and cells pre-treated with diethyldithiocarbamic acid, aminotriazole, and oxlalomalate, specific inhibitors of superoxide dismutase, catalase, and NADP(+)-dependent isocitrate dehydrogenase, respectively. Upon exposure to 1 mM 3-morpholinosydnomine N-ethylcarbamide (SIN-1), a generator of peroxynitrite through the reaction between nitric oxide and superoxide anion, to U937 cells, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in the inhibitor-treated cells as compared to the control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2'7'-dichlorodihydrofluorescin as well as the significant decrease in the intracellular GSH level in the inhibitor-treated U937 cells upon exposure to SIN-1. These results suggest that antioxidant enzymes play an important role in cellular defense against peroxynitrite-induced cell death.
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PMID:Antioxidant enzyme inhibitors enhance peroxynitrite-induced cell death in U937 cells. 1720 81

The intensity of lipid peroxidation (LPO), reduced and oxidized glutathione (GSH and GSSG) contents, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase (G-6-PDH), and NADP-isocitrate dehydrogenase (NADP-IDH) activities were studied in the heart of male rats exposed to two modes of intermittent hypoxic training (IHT): I-breathing in normobaric chamber with 7% O2 gas mixture for 5 min with 15 min normoxic intervals 4 times daily during 3 weeks; II-breathing by 12% O2 gas mixture in the same manner). After adaptation to hypoxia, the rats were subjected to 6h-immobilization stress. It has been shown that stress action after IHT (regime I) caused the increase in LPO and the shift of GSH/GSSG to disulfides. A disbalance in antioxidative defense system was determined by the decrease in glutatione peroxidase, G-6-PDH activities, and GSH content. The support of glutathione reductase activity under stress in this group with simultaneous decrease of enzyme activity in the pentose phosphate pathway was realized through the participation of NADP-IDH. Hypoxic training in regime II induced LPO decrease in the heart tissue after stress. The increase in the heart GSH content, optimal balance of glutathione-related enzymes in this group evidences for the dependence of adaptation effects on the vigor of hypoxic exposition. Our results suggest the active participation of glutathione system in the formation of adaptation reactions under the extreme factor influences through the action on intracellular red/ox potential as well as effectiveness of antioxidant defense.
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PMID:[Glutathione system adaptation to acute stress in the heart of rats during different regimes of hypoxia training]. 1798 18

The modulatory efficacy of capsaicin on lung mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, key citric acid cycle enzymes and respiratory chain enzymes during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice was studied. Elevations in mitochondrial LPO along with decrements in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and vitamin A), citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (alpha-KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and respiratory chain enzymes (NADH dehydrogenase and Cytochrome c oxidase) were observed in B(a)P (50mg/kg body weight) administered animals. CAP (10mg/kg body weight) pretreatment decreased lung mitochondrial LPO and augmented the activities of enzymic, non-enzymic antioxidants, citric acid cycle enzymes and respiratory chain enzymes to near normalcy revealing its chemoprotective function during B(a)P induced lung cancer.
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PMID:Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer. 1802 35

The mammalian antizyme (AZ) promotes ubiqutin-independent degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. This study shows that AZ suppression in human lung carcinoma A549 cells caused growth defects and death, but made the cells resistant to DNA damaging agents such as gamma-radiation and cisplatin. In these cells, the cellular redox potential (glutathione/glutathione disulfide [GSH/GSSG] ratio) was increased and thus intracellular reactive oxygen species were severely diminished, which might cause growth defects and cell death. The increase of cellular redox potential was mainly caused by dramatic increase of the cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP)(+)-dependent isocitrate dehydrogenase, which generates the reducing equivalents NADPH. In the AZ-suppressed cells, the hypoxia inducible factor 1alpha (HIF-1alpha) was also increased. As in other cases which showed an increment of HIF-1alpha and the cellular redox potential, the AZ-suppressed cells showed resistance to gamma-radiation and anticancer drugs. Therefore, these facts might be considered as important for the use of radio- and chemotherapy on tumor cells which show an unbalance in their polyamine levels.
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PMID:Antizyme suppression leads to an increment of the cellular redox potential and an induction of HIF-1alpha: its involvement in resistance to gamma-radiation. 1848 90

This study was undertaken to evaluate the preventive role of S-allyl cysteine sulphoxide (SACS) in isoproterenol (ISO)-induced cardiotoxicity in male Wistar rats. Myocardial infarction was induced by subcutaneous injection of ISO (150 mg/kg) once a day for 2 days. SACS (40 and 80 mg/kg) was given as pretreatment orally daily for a period of 35 days using an intragastric tube. SACS pretreatment significantly lowered thiobarbituric acid reactive substances (TBARS) and increased the activities of mitochondrial superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST), and the concentration of reduced glutathione (GSH) in myocardial infarcted rats. SACS pretreatment also increased significantly the levels of mitochondrial phospholipids and decreased the levels of mitochondrial cholesterol, free fatty acids (FFAs), triglycerides (TGs) and calcium, and the activity of xanthine oxidase (XOD) in heart. Further, the activities of isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), alpha-ketoglutarate dehydrogenase (alpha-KGDH), NADH-dehydrogenase, and cytochrome C-oxidase were significantly elevated in the mitochondrial fraction of the heart in the SACS-pretreated ISO-induced rats. Oral administration of SACS for a period of 35 days to the normal control rats did not show any significant effect. Histopathological studies of the myocardial tissue showed a protective role of SACS in the myocardial-infarcted rats. The effect at a dose of SACS 80 mg/kg was more effective than the dose 40 mg/kg. The results of the study conclude that SACS protect the mitochondria of the ISO-induced myocardial-infarcted rats.
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PMID:Preventive effect of S-allyl cysteine sulphoxide (Alliin) on mitochondrial dysfunction in normal and isoproterenol induced cardiotoxicity in male Wistar rats: a histopathological study. 1926 97

In an experimental model, it was shown that repetitive periods of hypoxia/reoxygenation (H/R) [5 cycles of 5 min hypoxia (12% O(2) in N(2) ) followed by 15 min normoxia, daily for three weeks] attenuated basal and stimulated in vitro lipid peroxidation, as well as H(2)O(2) production in liver and brain mitochondria of rats exposed to acute severe hypoxia. Adaptation to moderate H/R enhanced in mitochondria the production and activity of reactive oxygen species scavengers, such as glutathione, manganese superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase. It was demonstrated that the maintenance of GSH-redox cycle by activation of glutathione reductase and NADP(+) -dependent isocitrate dehydrogenase is an integral part of the biochemical adaptive mechanism of oxidative tolerance to new damaging factor. Brain mitochondria showed more sensitivity to oxidative stress than liver mitochondria, and long-lasting sessions of H/R affect differentially their pro-/antioxidant homeostasis.
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PMID:Effect of moderate hypoxia/reoxygenation on mitochondrial adaptation to acute severe hypoxia. 1958 28

Oxidative stress can play a key role in myocardial necrosis. The present study was designed to investigate the effect of alpha-mangostin (an antioxidant phytonutrient) on mitochondrial dysfunction and endothelial nitric oxide synthase (eNOS) expression during isoproterenol-induced myocardial necrosis in rats. Induction of rats with isoproterenol (ISO) (150 mg/kg body weight, intraperitoneally) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, and GSH), mitochondrial cytochromes (b, c, c1, and aa3), and adenosine triphosphate level. A marked elevation in mitochondrial lipid peroxidation was also observed in ISO-intoxicated rats. Pretreatment with alpha-mangostin (200 mg/kg body weight) orally for 8 days significantly attenuated these functional abnormalities and restored normal mitochondrial function, when compared to the ISO-intoxicated group of rats. Cardiac eNOS expression was assessed by Western blot. Cardiac eNOS expression and NO level were significantly suppressed in ISO-intoxicated rats. Pretreatment with alpha-mangostin extenuated ISO-induced diminution of eNOS expression and NO level. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings conclude the ameliorative potential of alpha-mangostin against ISO-induced biochemical and morphological changes in mitochondria, which might be mediated through the NO pathway and by its ability at quenching free radicals.
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PMID:Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana. 1979 27

E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (IQ) is a new quinoline derivative which has been reported as a haemoglobin degradation and ss-haematin formation inhibitor. The haemoglobin proteolysis induced by Plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. In this paper, we evaluated oxidative status in Plasmodium berghei-infected erythrocytes in the presence of IQ using chloroquine (CQ) as a control. After haemolysis, superoxide dismutase (SOD), catalase, glutathione cycle and NADPH + H+-dependent dehydrogenase enzyme activities were investigated. Lipid peroxidation was also assayed to evaluate lipid damage. The results showed that the overall activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were significantly diminished by IQ (by 53.5% and 100%, respectively). Glutathione peroxidase activity was also lowered (31%) in conjunction with a higher GSSG/GSH ratio. As a compensatory response, overall SOD activity increased and lipid peroxidation decreased, protecting the cells from the haemolysis caused by the infection. CQ shared most of the effects showed by IQ; however it was able to inhibit the activity of isocitrate dehydrogenase and glutathione-S-transferase. In conclusion, IQ could be a candidate for further studies in malaria research interfering with the oxidative status in Plasmodium berghei infection.
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PMID:Modification of oxidative status in Plasmodium berghei-infected erythrocytes by E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine. 1987 58


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