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Oxidative‐stress‐dependent up‐regulation of Bcl‐2 expression in the central nervous system of aged Fisher‐344 rats
Author(s) -
Kaufmann Joel A.,
Bickford Paula C.,
Taglialatela Giulio
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00118.x
Subject(s) - oxidative stress , nitrotyrosine , neurodegeneration , hippocampus , western blot , cerebellum , apoptosis , endocrinology , central nervous system , oxidative phosphorylation , lipid peroxidation , mitochondrion , medicine , chemistry , biology , neuroscience , microbiology and biotechnology , biochemistry , disease , nitric oxide synthase , nitric oxide , gene
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 O 2 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.