Modulation of caspase-3 activity by zinc ions and by the cell redox state.

Abstract:

:It is known that DNA fragmentation during apoptosis is controlled by a number of factors, a crucial step being the caspase-operated cleavage of ICAD, the DNase inhibitor. We have previously demonstrated that hydrogen peroxide-treated lymphocytes undergo apoptosis without formation of a DNA ladder; however, the use of micromolar amounts of a Zn(2+) chelator allowed DNA cleavage at internucleosomal sites. Such results were extended in the present work, thus allowing their framing into the events related to alterations in the redox state of the cell. Apoptosis in hydrogen peroxide-treated lymphocytes was found to occur with caspase-3 activation, but the enzyme activity was found to be impaired, thus affecting internucleosomal fragmentation as well as nuclear morphology. Caspase-3 activity was found to resume upon mild Zn(2+) chelation. These results provide as well an experimental model from which apoptotic events upstream and downstream of caspase-3 activity can be examined.

journal_name

Exp Cell Res

authors

Marini M,Frabetti F,Canaider S,Dini L,Falcieri E,Poirier GG

doi

10.1006/excr.2001.5222

keywords:

subject

Has Abstract

pub_date

2001-06-10 00:00:00

pages

323-32

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(01)95222-X

journal_volume

266

pub_type

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