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Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice.

ABSTRACT: Caspase-2 has been implicated in apoptosis and in non-apoptotic processes such as cell cycle regulation, tumor suppression and ageing. Using caspase-2 knockout (casp2(-/-)) mice, we show here that the putative anti-ageing role of this caspase is due in part to its involvement in the stress response pathway. The old casp2(-/-) mice show increased cellular levels of oxidized proteins, lipid peroxides and DNA damage, suggesting enhanced oxidative stress. Furthermore, murine embryonic fibroblasts from casp2(-/-) mice showed increased reactive oxygen species generation when challenged with pro-oxidants. Reduced activities of antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were observed in the old casp2(-/-) mice. Interestingly, in the old casp2(-/-) animals expression of FoxO1 and FoxO3a was significantly reduced, whereas p21 levels and the number of senescent hepatocytes were elevated. In contrast to young wild-type mice, the casp2(-/-) animals fed an on ethanol-based diet failed to show enhanced GSH-Px and SOD activities. Thus, caspase-2, most likely via FoxO transcription factors, regulates the oxidative stress response in vivo.

SUBMITTER: Shalini S

PROVIDER: S-EPMC3392626 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice.

Shalini S S Dorstyn L L Wilson C C Puccini J J Ho L L Kumar S S

Cell death and differentiation 20120217 8

Caspase-2 has been implicated in apoptosis and in non-apoptotic processes such as cell cycle regulation, tumor suppression and ageing. Using caspase-2 knockout (casp2(-/-)) mice, we show here that the putative anti-ageing role of this caspase is due in part to its involvement in the stress response pathway. The old casp2(-/-) mice show increased cellular levels of oxidized proteins, lipid peroxides and DNA damage, suggesting enhanced oxidative stress. Furthermore, murine embryonic fibroblasts fr ...[more]

PMID: 22343713

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Dataset Information

Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice.

Publications

Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice.

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