CHARACTERIZATION AND REGULATION OF COLD-INDUCED HEAT-SHOCK PROTEIN EXPRESSION IN MOUSE BROWN ADIPOSE-TISSUE

The accumulation of heat shock proteins (HSPs) after the exposure of c ells or organisms to-elevated temperatures is well established. It is also known that a variety of other environmental and cellular metaboli c stressors can induce HSP synthesis. However, few studies have invest igated the effect of cold temperature on HSP expression. Here we repor t that exposure of Institute of Cancer Research (ICR) mice to cold amb ient temperatures results in a tissue-selective induction of HSPs in b rown adipose tissue (BAT) coincident with the induction of mitochondri al uncoupling protein synthesis. Cold-induced HSP expression is associ ated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to he at-and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergi c agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to c old exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic r eceptors through, as yet, undetermined signal transduction pathways. T hermogenesis results from an increase in activity and synthesis of sev eral metabolic enzymes in BAT of animals exposed to cold challenge. Th e concomitant increase in HSPs may function to facilitate the transloc ation and activity of the enzymes involved in this process.