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

Understanding the functional genomics and proteomics of plasmodia underpins the development of new approaches to antimalarial chemotherapy. Although genome databanks (e.g. PlasmoDB) and biocomputing tools (e.g. PlasMit, PlasmoAP, PATS) are useful in providing a global albeit predictive view of the myriad of about 5000 genes, only 40% are annotated, with few cases of endorsed subcellular localizations of the corresponding proteins in animal models. Progress in plasmodial protein trafficking has been hampered by the lack of a simple yet reliable method for studying subcellular localization of plasmodial proteins. In this study, we have used a combination of fluorescent markers, organelle-specific probes, phase contrast microscopy, and confocal microscopy to locate a selection of signal peptides from 10 plasmodial proteins in CHO-K1 cells. These eukaryotic cells serve as an in vitro living system for studying the cellular destinations of four mitochondrial-targeted TCA cycle proteins (citrate synthase, CS; isocitrate dehydrogenase, ICDH; branched chain alpha-keto-acid dehydrogenase E1alpha subunit, BCKDH; succinate dehydrogenase flavoprotein-subunit, SDH), two nuclear-targeted proteins (histone deacetylase, HDAC; RNA polymerase, RPOL), two apicoplast-targeted proteins (pyruvate kinase 2, PK2; glutamate dehydrogenase, GDH), and two cytoplasmic resident proteins (malate dehydrogenase, MDH; glycerol kinase, GK). The respective localizations of these malarial proteins have complied with the selected molecular targets, viz. mitochondrial, nuclear and cytoplasmic. Interestingly, MDH that is widely known to be resident in eukaryotic mitochondria was found to be cytoplasmic, probably due to the absence of molecular target sequences. Since the localization of plasmodial proteins is central to the authentication of their pathophysiological roles, this experimental system will serve as a useful a priori approach.
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PMID:A relevant in vitro eukaryotic live-cell system for the evaluation of plasmodial protein localization. 1683 57

In order to investigate the metabolic poise of the elasmobranch rectal gland, we conducted two lines of experimentation. First, we examined the effects of feeding on plasma metabolites and enzyme activities from several metabolic pathways in several tissues of the dogfish shark, Squalus acanthias, after starvation and at 6, 20, 30 and 48 h post-feeding. We found a rapid and sustained ten-fold decrease in plasma beta-hydroxybutyrate at 6 h and beyond compared with starved dogfish, suggesting an upregulation in the use of this substrate, a decrease in production, or both. Plasma acetoacetate levels remain unchanged, whereas there was a slight and transient decrease in plasma glucose levels at 6 h. Several enzymes showed a large increase in activity post-feeding, including beta-hydroxybutyrate dehydrogenase in rectal gland and liver, and in rectal gland, isocitrate dehydrogenase, citrate synthase, lactate dehydrogenase, aspartate amino transferase, alanine amino transferase, glutamine synthetase and Na(+)/K(+) ATPase. Also notable in these enzyme measurements was the overall high level of activity in the rectal gland in general. For example, activity of the Krebs' TCA cycle enzyme citrate synthase (over 30 U g(-1)) was similar to activities in muscle from other species of highly active fish. Surprisingly, lactate dehydrogenase activity in the gland was also high (over 150 U g(-1)), suggesting either an ability to produce lactate anaerobically or use lactate as an aerobic fuel. Given these interesting observations, in the second aspect of the study we examined the ability of several metabolic substrates (alone and in combination) to support chloride secretion by the rectal gland. Among the substrates tested at physiological concentrations (glucose, beta-hydroxybutyrate, lactate, alanine, acetoacetate, and glutamate), only glucose could consistently maintain a viable preparation. Whereas beta-hydroxybutyrate could enhance gland activity when presented in combination with glucose, surprisingly it could not sustain chloride secretion when used as a lone substrate. Our results are discussed in the context of the in vivo role of the gland and mechanisms of possible upregulation of enzyme activities.
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PMID:Metabolic organization and effects of feeding on enzyme activities of the dogfish shark (Squalus acanthias) rectal gland. 1685 77

The present study investigated the protective efficacy of the novel preparation named as Kalpaamruthaa (KA, includes Semecarpus anacardium Linn nut milk extract (SA), dried powder of Phyllanthus emblica fruit and honey) on the peroxidative damage and abnormal antioxidant levels in the hepatic mitochondrial fraction of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma rats. Female Sprague-Dawley rats of weight 180+/-10 g were categorized into six groups. Three groups were administered DMBA (25 mg/rat dissolved in olive oil, orally) to induce mammary carcinoma. One of these groups received KA treatment (300 mg/kg b.wt., orally) and other group received SA (200 mg/kg b.wt., orally) for 14 days after 90 days of DMBA induction. Vehicle-treated control and drug control groups were also included. The hepatic mitochondrial fraction of untreated DMBA rats showed 2.96-fold increase in MDA content when compared to control rats and abnormal changes in the activities/levels of mitochondrial enzymic (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic (glutathione, vitamin C and vitamin E) antioxidants were observed. DMBA-treated rats also showed decline in the activities of mitochondrial enzymes such as succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase. In contrast, rats treated with SA and KA showed normal lipid peroxidation antioxidant defenses and mitochondrial enzymes, thereby showing the protection rendered by SA and KA. Although, KA treatment exhibited more profound effect in inhibiting DMBA-induced oxidative stress than sole SA treatment. Results of the study indicate that the anticarcinogenic activity of KA during DMBA-initiated mammary carcinogenesis is mediated through alteration of hepatic antioxidant status as well as modulation of TCA cycle enzymes. On the basis of the observed results, KA can be considered as a readily accessible, promising and novel cancer chemopreventive agent.
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PMID:Alteration of DMBA-induced oxidative stress by additive action of a modified indigenous preparation--Kalpaamruthaa. 1734 85

Mitochondria are an important intracellular source and target of reactive oxygen species. The life span of a species is thought to be determined, in part, by the rate of mitochondrial damage inflicted by oxygen free radicals during the course of normal cellular metabolism. In the present study, we have investigated the protective effect of squalene supplementation for 15 days and 30 days on energy status and antioxidant defense system in liver mitochondria of 18 young and 18 aged rats. The dietary supplementation of 2% squalene significantly minimized aging associated alterations in mitochondrial energy status by maintaining the activities of TCA cycle enzymes (isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase) and respiratory marker enzymes (NADH dehydrogenase and cytochrome-c-oxidase) at higher level in the liver mitochondria of aged rats compared with unsupplemented controls. It exerted an antioxidant effect by inhibiting mitochondrial lipid peroxidation (malondialdehyde) in liver of young and aged rats. Supplementation with squalene also maintained the mitochondrial antioxidant defense system at higher rate by increasing the level of reduced glutathione and the activities of glutathione-dependent antioxidant enzymes (glutathione peroxidase and glutathione-S-transferase) and antiperoxidative enzymes (superoxide dismutase and catalase) in the liver of young and aged rats. The results of this study provide evidence that dietary supplementation with squalene can improve liver mitochondrial function during aging and minimize the age-associated disorders in which reactive oxygen species are a major cause.
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PMID:Protective effect of dietary squalene supplementation on mitochondrial function in liver of aged rats. 1757 27

To identify the mechanisms underlying capacitation, we undertook a high-resolution differential proteomic analysis of pig sperm cells. Two-dimensional gel electrophoresis and subsequent MALDI-TOF mass spectrometry analyses led to identification of 56 differentially expressed proteins. After induction of capacitation in vitro, the well-established markers of the capacitation (lactadherin P47, acrosomal protein SP-10 precursor, prohibitin, proteasomes, DJ-1 protein and arylsulfatase-A) and TCA cycle proteins (isocitrate dehydrogenase, malate dehydrogenase and pyruvate dehydrogenase) were identified. During induction, cytochrome c expression via the p53 pathway increased, however apoptotic executors, such as caspase-3, decreased significantly. Therefore, we tested the hypothesis that cytochrome c upregulation in spermatozoa is capable of activating tyrosine phosphorylation for capacitation, rather than apoptosis. Exposure of sperm cells to soluble Na2CrO4 [Cr (VI)], which induces cytochrome c upregulation, caused a dose- and time-dependent increase in tyrosine phosphorylation of sperm proteins in non-capacitating medium. In contrast, supplementation of cyclosporin A, which blocks cytochrome c upregulation, inhibited tyrosine phosphorylation of sperm proteins. Furthermore, spermatozoa in capacitation medium or non-capacitation media supplemented with soluble Cr (VI) showed similar levels of capacitation. These findings indicate that differential expression of many of these proteins has previously been unrecognized in sperm cells incubated in capacitation medium also suggest that a gradual increase of cytochrome c during incubation to induce capacitation determines sperm cell fate, i.e., apoptosis or further development for fertilization.
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PMID:Cytochrome c upregulation during capacitation and spontaneous acrosome reaction determines the fate of pig sperm cells: linking proteome analysis. 1809 29

The amplification of gltA gene encoding citrate synthase of TCA cycle was required for the efficient conversion of acetyl-CoA, generated during vanillin production from ferulic acid, to CoA, which is essential for vanillin production. Vanillin of 1.98 g/L was produced from the E. coli DH5alpha (pTAHEF-gltA) with gltA amplification in 48 h of culture at 3.0 g/L of ferulic acid, which was about twofold higher than the vanillin production of 0.91 g/L obtained by the E. coli DH5alpha (pTAHEF) without gltA amplification. The icdA gene encoding isocitrate dehydrogenase of TCA cycle was deleted to make the vanillin producing E. coli utilize glyoxylate bypass which enables more efficient conversion of acetyl-CoA to CoA in comparison with TCA cycle. The production of vanillin by the icdA null mutant of E. coli BW25113 harboring pTAHEF was enhanced by 2.6 times. The gltA amplification of the glyoxylate bypass in the icdA null mutant remarkably increased the production rate of vanillin with a little increase in the amount of vanillin production. The real synergistic effect of gltA amplification and icdA deletion was observed with use of XAD-2 resin reducing the toxicity of vanillin produced during culture. Vanillin of 5.14 g/L was produced in 24 h of the culture with molar conversion yield of 86.6%, which is the highest so far in vanillin production from ferulic acid using recombinant E. coli.
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PMID:Directing vanillin production from ferulic acid by increased acetyl-CoA consumption in recombinant Escherichia coli. 1868 63

The growth and morphology as well as lipogenesis and activity of the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle were studied in the fungus Mucor circinelloides var. lusitanicus INMI grown at various concentrations of urea (nitrogen source) added to the medium in different modes. It was shown that the maximum lipid content in the biomass was observed at a low (0.5 g/l) concentration of the nitrogen source, whereas the highest content of gamma-linolenic acid in the lipids was detected at high (up to 4.0 g/l) concentrations of the nitrogen source. It was found that, when the feed-batch mode of nitrogen supply was used, the amount of gamma-linolenic acid in total fatty acids was higher (up to 35%) than in the case of a single administration of the same amount of nitrogen source to the medium. The differences in the fatty acid composition and the unsaturation degree of the lipids from different subcellular fractions were demonstrated. The mycelium from the culture grown after a single administration of the nitrogen source was deformed to a great extent. The activities of the TCA cycle enzymes, NAD-dependent isocitrate dehydrogenase (IDH), and malate dehydrogenase (MDH) were lower than in the case of the feed-batch mode of urea addition, whereas the activity of isocitrate lyase (ICL), the key enzyme of the glyoxylate cycle, was higher. The coupling of the cell metabolism and the lipid composition of fungal cells and the process of cell differentiation in fungi depending on the conditions of nitrogen supply is discussed.
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PMID:[Activity of NAD-dependent isocitrate dehydrogenase, isocitrate lyase, and malate dehydrogenase in Mucor circinelloides var. lusitanicus INMI under different modes of nitrogen supply]. 1882 70

To elucidate the metabolic characteristics of recombinant CHO cells expressing glutamine synthetase (GS) in the medium with or without glutamine, the concentrations of extra- and intracellular metabolites and the activities of key metabolic enzymes involved in glutamine metabolism pathway were determined. In the absence of glutamine, glutamate was utilized for glutamine synthesis, while the production of ammonia was greatly decreased. In addition, the expression of recombinant protein was increased by 18%. Interestingly, the intracellular glutamine maintained almost constant, independent of the presence of glutamine or not. Activities of glutamate-oxaloacetate aminotransferase (GOT), glutamate-pyruvate aminotransferase (GPT), and glutamate dehydrogenase (GDH) increased in the absence of glutamine. On the other hand, intracellular isocitrate and the activities of its downstream isocitrate dehydrogenase in the TCA cycle increased also. In combination with these two factors, a 8-fold increase in the intracellular alpha-ketoglutarate was observed in the culture of CHO-GS cells in the medium without glutamine.
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PMID:Metabolic characteristics of recombinant Chinese hamster ovary cells expressing glutamine synthetase in presence and absence of glutamine. 1900 91

The past decade has seen a revival of interest in the metabolic adaptations of tumours, named for their original discoverer, Otto Warburg. Warburg reported a high rate of glycolysis in tumours, and a concurrent defect in mitochondrial respiration. The rediscovery of Warburg's hypothesis coincided with the discovery of mitochondrial tumours suppressor genes that may conform to Warburg's hypothesis. Succinate dehydrogenase and fumarate hydratase are mitochondrial proteins of the TCA cycle and the respiratory chain and when mutated lead to tumours of the nervous system known as paragangliomas and pheochromocytomas, and in the case of fumarate hydratase, cutaneous and uterine leiomyomas and renal cell cancer. Recently a novel mitochondrial protein, SDHAF2 (SDH5), was also shown to be a paraganglioma-related tumour suppressor gene. Another mitochondrial and TCA cycle-related protein, isocitrate dehydrogenase 2 is, together with IDH1, frequently mutated in the brain tumour glioblastoma. There are currently many competing hypotheses on the role of these genes in tumourigenesis, but frequent themes are the stabilization of hypoxia inducible factor 1 and upregulation of genes involved in angiogenesis, glucose transport and glycolysis. Other postulated mechanisms include the inhibition of developmental apoptosis, altered gene expression due to histone deregulation and the acquisition of novel catalytic properties. Here we discuss these diverse hypotheses and highlight very recent findings on the possible effects of IDH gene mutations.
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PMID:Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? 2030 25


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