ADRENERGIC REGULATION OF THE HEAT-SHOCK RESPONSE IN BROWN ADIPOSE-TISSUE

One of several ways that cells respond to damage or stress is by the e xpression of a set of highly conserved proteins termed, heat shock pro teins (HSP). Induction of the heat shock response has been positively correlated with adaptation or protection of cells and tissues from the destructive effects of various types of stressors. Although heat can induce a generalized HSP response in most cells, the selective inducti on of HSP in specific cell populations by pharmacological agents may p rove therapeutically useful for the protection of organs or tissues at risk for damage. Results from our studies suggest that the HSP respon se is integrated with fundamental physiological stress responses and d emonstrate that distinct regulatory events couple neurotransmitter/hor mone-receptor interactions with HSP expression in mammalian tissues. W e demonstrate that the adrenergic receptor agonist, phenylephrine, ind uces HSP expression in brown adipose tissue (BAT). Apparently, this re sponse is mediated by alpha-adrenergic receptors in BAT because prazos in, but not propranolol, blocks HSP induction and hexamethonium is wit hout effect. Based on the transcripts induced and the magnitude of hea t shock element-binding activity, phenylephrine appears to induce HSP expression through unique transcriptional regulatory mechanisms. The p henylephrine-induced HSP response is not unique to BAT as we have foun d that HSP are induced in other tissues as well. In BAT, HSP may facil itate the thermogenic function of this tissue, however, their function in other tissues remains unclear. The results of this study character ize a model system where the heat shock response is differentially evo ked by a specific pharmacological agent and may aide in the developmen t of treatment strategies to selectively target HSP expression in vivo .