SODIUM-SALICYLATE DECREASES INTRACELLULAR ATP, INDUCES BOTH HEAT-SHOCK FACTOR-BINDING AND CHROMOSOMAL PUFFING, BUT DOES NOT INDUCE HSP-70 GENE-TRANSCRIPTION IN DROSOPHILA

Sodium salicylate has long been known to be an inducer of the heat sho ck puffs and presumably heat shock gene transcription in the polytene chromosomes of drosophila salivary gland cells. Stress induced transcr iption of the heat shock genes is mediated by the transcription factor known as Heat Shock Factor (HSF). In yeast, sodium salicylate has bee n reported to induce the DNA binding of HSF but not heat shock gene tr anscription itself, and similar findings have been reported in human c ells. This apparent discrepancy in the induction of certain aspects of the heat shock response between these organisms prompted us to carefu lly reexamine the induction of the heat shock response in Drosophila s alivary gland cells of third instar larvae and Drosophila tissue cultu re (SL2) cells. Sodium salicylate (3-30 mM) decreases intracellular AT P levels in SL2 cells and induces HSF binding activity in SL2 and sali vary gland cells in a dose dependent manner, Despite the induction of HSF binding and heat shock puffs in polytene chromosomes, we found no evidence for increased hsp 70 gene transcription suggesting that chrom osomal puffing and gene transcription may be separable events. Salicyl ate did not induce the HSF hyperphosphorylation that is normally assoc iated with HSF activation. Furthermore, salicylate (30 mM) prevented h eat-induced hyperphosphorylation of HSF and hsp 70 gene transcription indicating that salicylate's inhibitory effect on hsp 70 transcription may be independent of its effect on HSF binding activity. We propose that the reduction in intracellular ATP caused by the addition of sali cylate likely plays a role in the activation of HSF binding and the in hibition of both HSF hyperphosphorylation and hsp 70 gene transcriptio n.