Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice
Date
2012
Authors
Shalini, S.
Dorstyn, L.
Wilson, C.
Puccini, J.
Ho, L.
Kumar, S.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Cell Death and Differentiation, 2012; 19(8):1370-1380
Statement of Responsibility
S Shalini, L Dorstyn, C Wilson, J Puccini, L Ho and S Kumar
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Data source: Supplementary information, https://doi.org/10.1038/cdd.2012.13
Access Status
Rights
© 2012 Macmillan Publishers Limited