The University of Southampton
University of Southampton Institutional Repository

Zinc is a potent inhibitor of the apoptotic protease, caspase-3. a novel target for zinc in the inhibition of apoptosis

Perry, David K., Smyth, Mirrian J., Stennicke, Henning R., Salvesen, Guy S., Duriez, Patrick, Poirier, Guy G. and Hannun, Yusuf A. (1997) Zinc is a potent inhibitor of the apoptotic protease, caspase-3. a novel target for zinc in the inhibition of apoptosis The Journal of Biological Chemistry, 272, (30), pp. 18530-18533. (doi:10.1074/jbc.272.30.18530). (PMID:9228015).

Record type: Article


The prevention of apoptosis by Zn2+ has generally been attributed to its inhibition of an endonuclease acting in the late phase of apoptosis. In this study we investigated the effect of Zn2+ on an earlier event in the apoptotic process, the proteolysis of the "death substrate" poly(ADP-ribose) polymerase (PARP). Pretreatment of intact Molt4 leukemia cells with micromolar concentrations of Zn2+ caused an inhibition of PARP proteolysis induced by the chemotherapeutic agent etoposide. Using a cell-free system consisting of purified bovine PARP as a substrate and an apoptotic extract or recombinant caspase-3 as the PARP protease, Zn2+ inhibited PARP proteolysis in the low micromolar range. To rule out an effect of Zn2+ on PARP, a protein with two zinc finger domains, we used recombinant caspase-3 and a chromogenic tetrapeptide substrate containing the caspase-3 cleavage site. In this system, Zn2+ inhibited caspase-3 with an IC50 of 0.1 microM. These results identify caspase-3 as a novel target of Zn2+ inhibition in apoptosis and suggest a regulatory role for Zn2+ in modulating the upstream apoptotic machinery.

Full text not available from this repository.

More information

Published date: 25 July 1997


Local EPrints ID: 164823
ISSN: 0021-9258
PURE UUID: 4087a6de-aa68-4f2d-80de-d72ee9529a91

Catalogue record

Date deposited: 04 Oct 2010 14:27
Last modified: 18 Jul 2017 12:28

Export record



Author: David K. Perry
Author: Mirrian J. Smyth
Author: Henning R. Stennicke
Author: Guy S. Salvesen
Author: Patrick Duriez
Author: Guy G. Poirier
Author: Yusuf A. Hannun

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.