期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 287, 期 3, 页码 F492-F500出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00083.2004
关键词
ischemia; renal tubule
Apoptosis has been implicated in ischemic renal injury. Thus one strategy of renal protection is to antagonize apoptosis. However, apoptosis inhibitory approaches remain to be fully explored. Zn2+ has long been implicated in apoptosis inhibition; but systematic analysis of the inhibitory effects of Zn2+ is lacking. Moreover, whether Zn2+ blocks renal cell apoptosis following ischemia is unknown. Here, we demonstrate that Zn2+ is a potent apoptosis inhibitor in an in vitro model of renal cell ischemia. ATP depletion induced apoptosis in cultured renal tubular cells, which was accompanied by caspase activation. Zn2+ at 10 muM inhibited both apoptosis and caspase activation, whereas Co2+ was without effect. In ATP-depleted cells, Zn2+ partially prevented Bax activation and cytochrome c release from mitochondria. In isolated cell cytosol, Zn2+ blocked cytochrome c-stimulated caspase activation at low-micromolar concentrations. In addition, Zn2+ could directly antagonize the enzymatic activity of purified recombinant caspases. We conclude that Zn2+ is a potent inhibitor of apoptosis in renal tubular cells following ATP depletion. Zn2+ blocks apoptosis at multiple steps including Bax activation, cytochrome c release, apoptosome function, and caspase activation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据