Mitochondrial isocitrate dehydrogenase protects human neuroblastoma SH-SY5Y cells against oxidative stress

Sun J. Kim, Tae Y. Yune, Ching T. Han, Young C. Kim, Young J. Oh, George J. Markelonis, Tae H. Oh

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 anti-oxidants, 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 (Δψm) was correlated with the time of mitochondrial Mcl-1 release; the loss of Δψm 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.

Original languageEnglish
Pages (from-to)139-152
Number of pages14
JournalJournal of Neuroscience Research
Volume85
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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