Molecular failure of apoptosis: inappropriate cell survival and mutagenesis?

Abstract:

:Since cell death by apoptosis is achieved through complex interactions between numerous molecular components, cells may fail to die when stimulated because of molecular abnormalities in the apoptosis pathway or in its control mechanisms. Such inappropriate cell survival is well established when apoptosis is suppressed by elevated expression of bcl-2, at least for some cell types. Many cells undergo apoptosis at moderate levels of DNA damage and suppression of such apoptosis might be expected to increase the rate of mutation because of the persistence of cells with damaged DNA. We and others have now confirmed this prediction in bcl-2 transfected cells. Suppression of the apoptosis pathway can only lead to inappropriate cell survival if it relates to events before the cell becomes committed to die. We have analyzed this question for agents that inhibit the caspases, the site-specific proteases which form the biochemical core of the process of apoptosis. We have shown that inhibition of certain caspases does lead to the survival of Jurkat human T-cells induced to undergo Fas-mediated apoptosis.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Williams GT,Critchlow MR,Hedge VL,O'Hare KB

doi

10.1016/s0378-4274(98)00343-9

keywords:

subject

Has Abstract

pub_date

1998-12-28 00:00:00

pages

485-9

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(98)00343-9

journal_volume

102-103

pub_type

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