Silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase gene enhances selenite-induced apoptosis.
Selenium has been shown to play a chemopreventive role in human cancer, presumably by inducing tumour cell apoptosis. Selenite is thought to induce oxidative stress by the generation of the superoxide anion and catalysing the oxidation of thiol groups. It has previously been 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 investigating 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.
Kil
In Sup
IS
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.
Chung
Kyu Ho
KH
Park
Jeen-Woo
JW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002469:Cell Separation; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D005434:Flow Cytometry; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007521:Isocitrate Dehydrogenase / Q000187:drug effects / Q000235:genetics*; D034741:RNA, Small Interfering; D018038:Sodium Selenite / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D034741:RNA, Small Interfering; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D018038:Sodium Selenite