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 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number3 56-3
DOIs
StatePublished - Sep 1 2004

Fingerprint

Adenosine Triphosphate
Apoptosis
Kidney
Caspases
Cytochromes c
Apoptosomes
Ischemia
Cytosol
Mitochondria
Wounds and Injuries

Keywords

  • Ischemia
  • Renal tubule

ASJC Scopus subject areas

  • Physiology

Cite this

Inhibition of apoptosis by Zn2+ in renal tubular cells following ATP depletion. / Wei, QingQing; Wang, Jinzhao; Wang, Mong-Heng; Yu, Fushin; Dong, Zheng.

In: American Journal of Physiology - Renal Physiology, Vol. 287, No. 3 56-3, 01.09.2004.

Research output: Contribution to journalArticle

@article{f9bf5c846e9d42aa8df208e26b09714e,
title = "Inhibition of apoptosis by Zn2+ in renal tubular cells following ATP depletion",
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.",
keywords = "Ischemia, Renal tubule",
author = "QingQing Wei and Jinzhao Wang and Mong-Heng Wang and Fushin Yu and Zheng Dong",
year = "2004",
month = "9",
day = "1",
doi = "10.1152/ajprenal.00083.2004",
language = "English (US)",
volume = "287",
journal = "American Journal of Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3 56-3",

}

TY - JOUR

T1 - Inhibition of apoptosis by Zn2+ in renal tubular cells following ATP depletion

AU - Wei, QingQing

AU - Wang, Jinzhao

AU - Wang, Mong-Heng

AU - Yu, Fushin

AU - Dong, Zheng

PY - 2004/9/1

Y1 - 2004/9/1

N2 - 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.

AB - 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.

KW - Ischemia

KW - Renal tubule

UR - http://www.scopus.com/inward/record.url?scp=4644262372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644262372&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00083.2004

DO - 10.1152/ajprenal.00083.2004

M3 - Article

C2 - 15113746

AN - SCOPUS:4644262372

VL - 287

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1931-857X

IS - 3 56-3

ER -