Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fisher-344 rats

Joel A. Kaufmann, Paula C. Bickford, Giulio Taglialatela

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Oxidative stress has been shown to play a role in aging and in neurodegenerative disorders. Some of the consequences of oxidative stress are DNA base modifications, lipid peroxidation, and protein modifications such as formation of carbonyls and nitrotyrosine. These events may play a role in apoptosis, another factor in aging and neurodegeneration, in response to uncompensated oxidative stress. Bcl-2 is a mitochondrial protein that protects neurons from apoptotic stimuli including oxidative stress. Using immunohistochemistry and western blot analysis, here we show that Bcl-2 is up-regulated in the hippocampus and cerebellum of aged (24 months) Fisher 344 rats. Treatment with the free radical spin trap N-tert-butyl-α-phenylnitrone (PBN) effectively reverses this age-dependent Bcl-2 up-regulation indicating that this response is redox sensitive. This conclusion was further supported by inducing the same regional Bcl-2 up-regulation in young (3 months) Fisher 344 rats exposed to 100% normobaric O2 for 48 h. Our results indicate that Bcl-2 expression is increased in the aged brain, possibly as a consequence of oxidative stress challenges. These results also illustrate the effectiveness of antioxidants in reversing age-related changes in the CNS and support further research to investigate their use in aging and in age-related neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)1099-1108
Number of pages10
JournalJournal of neurochemistry
Volume76
Issue number4
DOIs
StatePublished - Mar 3 2001

Keywords

  • Aging
  • Bcl-2
  • CNS
  • Oxidative stress
  • PBN

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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