Glucocorticoids regulate protein synthesis in hippocampal slices under mild heat shock conditions

Abstract

Glucocorticoid hormones potentiate the toxic effects of neuronal stressors. Alteration of gene expression by glucocorticoids could contribute to neuronal susceptibility by downregulating the synthesis of proteins necessary to adapt to challenge. Using heat shock of hippocampal slices as a model for cellular insult, protein synthesis has been examined in response to acute glucocorticoid administration to rats. Incubation of hippocampal slices at 39 degrees C produces a heat-shock pattern of protein synthesis in that total incorporation of labeled amino acid is diminished, whereas synthesis of the major heat-shock proteins, HSP90 and HSP70, is increased. Prior administration of corticosterone to rats does not affect subsequent synthesis of HSP90 or HSP70 in slices. However, at 4 or 24 h following a single corticosterone injection, the synthesis of two acidic proteins is found to be altered: a 25-kDa protein is downregulated in the nuclear and synaptosomal-mitochondrial fraction of the hippocampus, and a 47-kDa protein is downregulated in all three fractions of the hippocampus, cortex, and cerebellum. These effects are mimicked by administration of RU-28362, a specific glucocorticoid (GR or Type II) receptor agonist. Since decreased synthesis of p25 and p47 is the only glucocorticoid-mediated response observed in slices under heat-shock conditions, these proteins may be related to the adaptation to heat shock.