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 commo nly been analyzed using tissue culture systems, with less investigatio n 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 physio logically 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 c erebellum showing the strongest signal. Supershift experiments with an tibodies specific to HSF1 and HSF2 demonstrated that the signal reflec ted activation of HSF1. Western blot analysis showed that cerebellum e xhibited high levels of HSF1 protein. (C) 1996 Wiley-Liss, Inc.