Glucocorticoids regulate the synthesis of HSP27 in rat brain slices

Using mild heat shock of rat brain slices as a model for cellular insult, corticosteroid-mediated regulation of protein synthesis has been investigated. Following a single in vivo injection of rats with corticosterone or the Type II glucocorticoid receptor agonist, RU-28362, synthesis of a 28 kDa protein is elevated in cerebellar slices which are subsequently incubated in vitro at 39 degrees C for 3 h. Immunoblotting of proteins subsequent to separation by two-dimensional gel electrophoresis has identified this glucocorticoid-sensitive protein to be the small molecular weight heat-shock protein, HSP27. Synthesis of the major heat-shock proteins, HSP70 and HSP90, is not glucocorticoid-sensitive. When animals are sacrificed at either 4 h following an aldosterone injection or at 24 h following a corticosterone injection, the synthesis of HSP27 in cerebellar slices is decreased. Treatment of adrenalectomized rats with either corticosterone, RU-28362 or aldosterone produces increased synthesis of HSP27. With duration of heat shock, there is a transient increase in the synthesis of HSP27 after 2 h at 39 degrees C in slices from the cerebral cortex, with a more sustained synthesis of HSP27 in cerebellar slices. In hippocampal slices, HSP27 is rarely present. The upregulated synthesis of HSP27 in the cerebellum following an acute exposure to stress-like elevations in corticosterone titers may contribute to the relative resistance of this brain region to cellular insults.