TY - JOUR
T1 - Caspase-3 protects stressed organs against cell death
AU - Khalil, Hadi
AU - Peltzer, Nieves
AU - Walicki, Joël
AU - Yang, Jiang Yan
AU - Dubuis, Gilles
AU - Gardiol, Noémie
AU - Held, Werner
AU - Bigliardi, Paul
AU - Marsland, Benjamin
AU - Liaudet, Lucas
AU - Widmann, Christian
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00774-12
DO - 10.1128/MCB.00774-12
M3 - Article
C2 - 22949508
AN - SCOPUS:84868698549
SN - 0270-7306
VL - 32
SP - 4523
EP - 4533
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 22
ER -