In vivo activation of neural heat shock transcription factor HSF1 by a physiologically relevant increase in body temperature

Molecular mechanisms which underlie the heat shock response have commonly been analyzed using tissue culture systems, with less investigation of the intact mammal. In tissue culture, a temperature elevation of 5 degrees C is required to activate mammalian heat shock transcription factor 1 (HSF1) to the DNA-binding form. We demonstrate that a physiologically relevant increase in body temperature of 2.5 +/- 0.2 degrees C, similar to that attained during fever reactions, is sufficient to activate HSF1 in the rabbit nervous system. Maximal HSF activation, as measured by gel mobility shift assay, was attained at 1 hr with the cerebellum showing the strongest signal. Supershift experiments with antibodies specific to HSF1 and HSF2 demonstrated that the signal reflected activation of HSF1. Western blot analysis showed that cerebellum exhibited high levels of HSF1 protein.