PHARMACOLOGICAL INDUCTION OF HEAT-SHOCK-PROTEIN-68 SYNTHESIS IN CULTURED RAT ASTROCYTES

The induction of the highly inducible 70-kDa heat shock protein (HSP 7 0) is associated with thermotolerance and survival from many other typ es of stress. This investigation studied the pharmacological induction of HSP 68 (HSP 68 is the rat homolog of human HSP 70) by 1,10-phenant hroline in cultured rat astrocytes under conditions that activated hea t shock transcription factor-1 without inducing HSP 68 synthesis. Two conditions that activate heat shock transcription factor-1 and promote its binding to the heat shock element without subsequent transcriptio n of HSP 68 mRNA, intracellular acidosis and exposure to salicylate, s howed synthesis of HSP 68 when 1,10-phenanthroline was added to cultur e medium after the activation of heat shock transcription factor-1. 1, 10-phenanthroline mimicked heat shock by inducing HSP 68 mRNA and prot ein under both conditions. 1,10-phenanthroline added alone to culture medium did not induce the synthesis of HSP 68 or activate heat shock t ranscription factor-1. These findings strongly suggest a multistep act ivation for HSP 68 synthesis and also demonstrate that the synthesis o f HSP 68 can be pharmacologically regulated.