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Type: Journal article
Title: Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice
Author: Shalini, S.
Dorstyn, L.
Wilson, C.
Puccini, J.
Ho, L.
Kumar, S.
Citation: Cell Death and Differentiation, 2012; 19(8):1370-1380
Publisher: Nature Publishing Group
Issue Date: 2012
ISSN: 1350-9047
Statement of
S Shalini, L Dorstyn, C Wilson, J Puccini, L Ho and S Kumar
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.
Keywords: oxidative stress
Rights: © 2012 Macmillan Publishers Limited
DOI: 10.1038/cdd.2012.13
Appears in Collections:Aurora harvest
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