Activation of heat shock protein (hsp)70 and proto-oncogene expression by α1 adrenergic agonists in rat aorta with age

Abstract

Induction of heat shock proteins (hsp) most likely is a homeostatic mechanism in response to metabolic and environmental insults. We have investigated signal transduction mechanisms involved in α1 adrenergic receptor stimulation of hsp70 gene expression in isolated aortas with age. We found that α1 adrenergic agonists directly induced hsp70 mRNA in rat aorta in vitro; the α1 selective antagonist prazosin blocked this effect whereas chloroethylclonidine, an antagonist which has some selectivity for α(1B) receptors, was ineffective. This response was insensitive to pertussis toxin and was partially blocked by the protein kinase C inhibitor H7. Removal of extracellular calcium attenuated induction of hsp70 mRNA but not the induction of c-fos or c-myc. The induction of hsp70 mRNA by either norepinephrine or by phorbol dibutyrate was blunted in aortas from old (24- 27 mo) rats whereas c-fos responses were not diminished in the older vessels. The hsp70 response to elevated temperature (42°C) was not changed with age. Activation of hsp70 expression most likely involves a pertussis toxin insensitive G protein which activates protein kinase C, and requires extracellular calcium. With age, hsp70 gene expression induced by stimulation of α1 adrenergic receptors is markedly attenuated, which could modify responses to stress or vascular injury with aging.