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 shock puffs and presumably heat shock gene transcription in the polytene chromosomes of Drosophila salivary gland cells. Stress-induced transcription of the heat shock genes is mediated by the transcription factor known as Heat Shock Factor (HSF). In yeast, sodium salicylate has been reported to induce the DNA binding of HSF but not heat shock gene transcription itself, and similar findings have been reported in human cells. This apparent discrepancy in the induction of certain aspects of the heat shock response between these organisms prompted us to carefully reexamine the induction of the heat shock response in Drosophila salivary gland cells of third instar larvae and Drosophila tissue culture (SL2) cells. Sodium salicylate (3-30 mM) decreases intracellular ATP levels in SL2 cells and induces HSF binding activity in SL2 and salivary 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 chromosomal puffing and gene transcription may be separable events. Salicylate did not induce the HSF hyperphosphorylation that is normally associated with HSF activation. Furthermore, salicylate (30 mM) prevented heat-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 salicylate likely plays a role in the activation of HSF binding and the inhibition of both HSF hyperphosphorylation and hsp 70 gene transcription.