Activation of heat shock protein (hsp)70 and proto-oncogene expression by alpha(1) adrenergic agonists in rat aorta with age

被引:41
作者
Chin, JH
Okazaki, M
Hu, ZW
Miller, JW
Hoffman, BB
机构
[1] VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,PALO ALTO,CA 94304
[2] STANFORD UNIV,DEPT MED,SCH MED,PALO ALTO,CA 94304
关键词
catecholamines; alpha(1) adrenergic receptors; aging; heat shock proteins; vascular smooth muscle;
D O I
10.1172/JCI118674
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 alpha(1) adrenergic receptor stimulation of hsp70 gene expression in isolated aortas with age. We found that alpha(1) adrenergic agonists directly induced hsp70 mRNA in rat aorta in vitro; the alpha(1) selective antagonist prazosin blocked this effect whereas chloroethylclonidine, an antagonist which has some selectivity for alpha(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) Eats whereas c-fos responses were not diminished in the older vessel, 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 alpha(1) adrenergic receptors is markedly attenuated, which could modify responses to stress or vascular injury with aging. (J. Clin, Invest. 1996. 97:2316-2323.)
引用
收藏
页码:2316 / 2323
页数:8
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