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)

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

Staurosporine induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, it was demonstrated that the control of cellular redox balance and the defense against oxidative damage is one of the primary functions of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) by supplying NADPH for antioxidant systems. The present report shows that silencing of IDPc expression in HeLa cells greatly enhances apoptosis induced by staurosporine. Transfection of HeLa cells with an IDPc small interfering RNA (siRNA) markedly decreased activity of IDPc, enhancing the susceptibility of staurosporine-induced apoptosis reflected by DNA fragmentation, cellular redox status and the modulation of apoptotic marker proteins. These results indicate that IDPc may play an important role in regulating the apoptosis induced by staurosporine and the sensitizing effect of IDPc siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy.
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PMID:Silencing of cytosolic NADP(+)-dependent isocitrate dehydrogenase by small interfering RNA enhances the sensitivity of HeLa cells toward staurosporine. 1920 69