Lee Su-Min, Park Sin Young, Shin Seoung Woo, Kil In Sup, Yang Eun Sun, Park Jeen-Woo
College of Natural Sciences, Kyungpook National University, Taegu, Korea.
Free Radic Res. 2009 Feb;43(2):165-73. doi: 10.1080/10715760802653661.
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.
星形孢菌素可诱导活性氧的产生，活性氧在凋亡性细胞死亡中起重要的致病作用。最近有研究表明，通过为抗氧化系统提供NADPH，控制细胞氧化还原平衡和抵御氧化损伤是胞质NADP(+)-依赖性异柠檬酸脱氢酶（IDPc）的主要功能之一。本报告显示，HeLa细胞中IDPc表达的沉默极大地增强了星形孢菌素诱导的细胞凋亡。用IDPc小干扰RNA（siRNA）转染HeLa细胞显著降低了IDPc的活性，增强了由DNA片段化、细胞氧化还原状态和凋亡标志物蛋白的调节所反映的对星形孢菌素诱导凋亡的敏感性。这些结果表明，IDPc可能在调节星形孢菌素诱导的凋亡中起重要作用，且IDPc siRNA对HeLa细胞凋亡性细胞死亡的致敏作用为开发癌症化疗修饰剂提供了可能性。
