Caspase-3 Protects Stressed Organs against Cell Death.

Details

Ressource 1Download: Mol. Cell. Biol.-2012-Khalil-4523-33 (1).pdf (4595.03 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_3A213E3293BE
Type
Article: article from journal or magazin.
Collection
Publications
Title
Caspase-3 Protects Stressed Organs against Cell Death.
Journal
Molecular and Cellular Biology
Author(s)
Khalil H., Peltzer N., Walicki J., Yang J.Y., Dubuis G., Gardiol N., Held W., Bigliardi P., Marsland B., Liaudet L., Widmann C.
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
32
Number
22
Pages
4523-4533
Language
english
Abstract
The ability to generate appropriate defense responses is crucial for the survival of an organism exposed to pathogenesis-inducing insults. However, the mechanisms that allow tissues and organs to cope with such stresses are poorly understood. Here we show that caspase-3-knockout mice or caspase inhibitor-treated mice were defective in activating the antiapoptotic Akt kinase in response to various chemical and environmental stresses causing sunburns, cardiomyopathy, or colitis. Defective Akt activation in caspase-3-knockout mice was accompanied by increased cell death and impaired survival in some cases. Mice homozygous for a mutation in RasGAP that prevents its cleavage by caspase-3 exhibited a similar defect in Akt activation, leading to increased apoptosis in stressed organs, marked deterioration of their physiological functions, and stronger disease development. Our results provide evidence for the relevance of caspase-3 as a stress intensity sensor that controls cell fate by either initiating a RasGAP cleavage-dependent cell resistance program or a cell suicide response.
Pubmed
Web of science
Open Access
Yes
Create date
29/11/2012 18:57
Last modification date
20/08/2019 14:29
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