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 expression of a set of highly conserved proteins termed, heat shock proteins (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 induction of HSP in specific cell populations by pharmacological agents may prove therapeutically useful for the protection of organs or tissues at risk for damage. Results from our studies suggest that the HSP response is integrated with fundamental physiological stress responses and demonstrate that distinct regulatory events couple neurotransmitter/hormone-receptor interactions with HSP expression in mammalian tissues. We demonstrate that the adrenergic receptor agonist, phenylephrine, induces HSP expression in brown adipose tissue (BAT). Apparently, this response is mediated by alpha-adrenergic receptors in BAT because prazosin, but not propranolol, blocks HSP induction and hexamethonium is without effect. Based on the transcripts induced and the magnitude of heat shock element-binding activity, phenylephrine appears to induce HSP expression through unique transcriptional regulatory mechanisms. The phenylephrine-induced HSP response is not unique to BAT as we have found that HSP are induced in other tissues as well. In BAT, HSP may facilitate the thermogenic function of this tissue, however, their function in other tissues remains unclear. The results of this study characterize a model system where the heat shock response is differentially evoked by a specific pharmacological agent and may aide in the development of treatment strategies to selectively target HSP expression in vivo.
Matz
J M
JM
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine, Grand Forks, USA.
LaVoi
K P
KP
Blake
M J
MJ
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D015870:Gene Expression / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010656:Phenylephrine / Q000494:pharmacology*
D018840:HSP70 Heat-Shock Proteins; D010656:Phenylephrine