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

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

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53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1370-1380
Number of pages11
JournalCell Death and Differentiation
Volume19
Issue number8
DOIs
Publication statusPublished - 1 Aug 2012
Externally publishedYes

Keywords

  • ageing
  • antioxidant
  • caspases
  • oxidative stress
  • ROS

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