Inhibition of apoptosis by Zn2+ in renal tubular cells following ATP depletion

Qingqing Wei, Jinzhao Wang, Mong Heng Wang, Fushin Yu, Zheng Dong

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 Zn 2+ 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 μM 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.

Original languageEnglish (US)
Pages (from-to)F492-F500
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number3 56-3
DOIs
StatePublished - Sep 1 2004

Keywords

  • Ischemia
  • Renal tubule

ASJC Scopus subject areas

  • Physiology
  • Urology

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