Cytosolic NADP(+)-dependent isocitrate dehydrogenase regulates cadmium-induced apoptosis.
Cadmium ions have a high affinity for thiol groups. Therefore, they may disturb many cellular functions. We recently reported that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) functions as an antioxidant enzyme to supply NADPH, a major source of reducing equivalents to the cytosol. Cadmium decreased the activity of IDPc both as a purified enzyme and in cultured cells. In the present study, we demonstrate that the knockdown of IDPc expression in HEK293 cells greatly enhances apoptosis induced by cadmium. Transfection of HEK293 cells with an IDPc small interfering RNA significantly decreased the activity of IDPc and enhanced cellular susceptibility to cadmium-induced apoptosis as indicated by the morphological evidence of apoptosis, DNA fragmentation and condensation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. Taken together, our results suggest that suppressing the expression of IDPc enhances cadmium-induced apoptosis of HEK293 cells by increasing disruption of the cellular redox status.
Shin
Seoung Woo
SW
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
Kil
In Sup
IS
Park
Jeen-Woo
JW
D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology*; D053148:Caspase 3 / Q000502:physiology; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering; D002104:Cadmium; D009249:NADP; D007521:Isocitrate Dehydrogenase; D053148:Caspase 3