| First Author | Shalini S | Year | 2012 |
| Journal | Cell Death Differ | Volume | 19 |
| Issue | 8 | Pages | 1370-80 |
| PubMed ID | 22343713 | Mgi Jnum | J:204632 |
| Mgi Id | MGI:5532904 | Doi | 10.1038/cdd.2012.13 |
| Citation | Shalini S, et al. (2012) Impaired antioxidant defence and accumulation of oxidative stress in caspase-2-deficient mice. Cell Death Differ 19(8):1370-80 |
| abstractText | 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. |
