Regulation of pp60(c-src) synthesis in rat hippocampal slices by in vitro ischemia and glucocorticoid administration.
Corticosteroids, released from the adrenal gland in response to stress, bind to receptors that act as transcription factors to alter gene expression and, subsequently, protein synthesis. Using [(35)S]-methionine-cysteine incorporation to measure protein synthesis in hippocampal slices incubated under ischemic conditions, synthesis of 60 kDa and 78 kDa proteins decreases 4 hr after in vivo administration of corticosterone to rats. The former protein has been identified by immunoblotting and immunoprecipitation to be the proto-oncogene, pp60(c-src). In the absence of prior glucocorticoid administration, ischemic conditions increase the amount of immunoreactive pp60(c-src) in membranes of hippocampal slices. Chronic exposure to elevated titers of glucocorticoids has been demonstrated to result in cell loss as well as in reduced neuronal plasticity and regeneration. Given the involvement of pp60(c-src) in synaptic plasticity and cell growth, glucocorticoid-mediated reduction in its synthesis is a potential molecular marker for stress-induced alterations in brain function.
Barr
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Departments of Neurology and Biochemistry/Molecular Biology, Medical College of Ohio, 3120 Glendale Avenue, Toledo, OH 43614-5809, USA.
Dokas
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LA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D016392:Proto-Oncogene Proteins pp60(c-src); D003345:Corticosterone