Increased HSF activation in muscles with a high constitutive Hsp70 expression.

Stress-induced transcriptional regulation of the Hsps is mediated by trimerization and binding of a pre-existing heat shock transcription factor (HSF1) to a specific DNA sequence located in the 5' region of hsp genes, known as the heat shock element. Hsp70 has been implicated in regulating the activation of the HSF and, according to cell culture models, high steady-state levels of Hsp70 are inversely correlated with HSF activation. To determine if this applies in an intact animal, muscles of the rat hindlimb which differ in the constitutive expression of Hsp70, were assessed for HSF activation following heat shock. Mobility shift gel analyses demonstrated that HSF activation was detectable in extracts from all muscles following heat shock regardless of Hsp70 content. However, muscles comprised predominantly of slow/Type I fibers (soleus) demonstrated a greater HSF activation, as well as a faster HSF activation and inactivation, than muscles comprised predominantly of fast/Type II fibers (white gastrocnemius). In addition, muscles pretreated by two heat shocks (24 h apart) demonstrated a stronger HSF activation than muscles subjected to only one heat shock. Thus, results from cell culture models demonstrating that tissue levels of Hsp70 are inversely correlated with HSF activation, may not apply to the muscles of an intact animal.