Activation of heat shock protein (hsp)70 and proto-oncogene expression by alpha1 adrenergic agonist in rat aorta with age.
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 alpha1, adrenergic receptor stimulation of hsp7O gene expression in isolated aortas with age. We found that alpha1 adrenergic agonists directly induced hsp70 mRNA in rat aorta in vitro; the alpha1, selective antagonist prazosin blocked this effect whereas chloroethylclonidine, an antagonist which has some selectivity for alpha1B 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 degrees 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 alpha1 adrenergic receptors is markedly attenuated, which could modify responses to stress or vascular injury with aging.
Chin
J H
JH
Department of Medicine, Stanford University School of Medicine and Geriatric Research, Palo Alto, California 94304, USA.
Okazaki
M
M
Hu
Z W
ZW
Miller
J W
JW
Hoffman
B B
BB
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C; D009638:Norepinephrine