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Silencing of mitochondrial NADP+‐dependent isocitrate dehydrogenase gene enhances selenite‐induced apoptosis
Author(s) -
Park JeenWoo,
Kil In Sup,
Chung Kyu Ho
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.703.4
Subject(s) - apoptosis , hela , isocitrate dehydrogenase , dna fragmentation , oxidative stress , gene silencing , transfection , mitochondrion , chemistry , microbiology and biotechnology , fragmentation (computing) , superoxide , programmed cell death , biology , biochemistry , cell , enzyme , gene , ecology
Selenium has been shown to play a chemopreventive role in human cancer, presumably by inducing tumor cell apoptosis. Selenite is thought to induce oxidative stress by the generation of the superoxide anion and catalyzing the oxidation of thiol groups. We previously reported that control of the mitochondrial redox balance is a primary function of mitochondrial NADP+‐dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. When we investigated whether IDPm would be a vulnerable target of selenite, the loss of enzyme activity was observed. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm and enhanced cells?susceptibility of selenite‐induced apoptosis as indicated by morphological evidence of apoptosis, DNA fragmentation, and the modulation of mitochondrial function and apoptotic marker proteins. These results suggest that IDPm siRNA sensitizes HeLa cells to selenite‐induced apoptotic cell death presumably through the perturbation of the cellular redox status.