期刊
CIRCULATION RESEARCH
卷 86, 期 7, 页码 760-767出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.86.7.760
关键词
Ca2+ sparks; CREB; gene expression; receptors, ryanodine; arterial smooth muscle
资金
- NHLBI NIH HHS [HL44455] Funding Source: Medline
Pathological changes of the vasculature are characterized by changes in Ca2+ handling and alterations in gene expression. In neurons and other cell types, [Ca2+](i) often drives changes in gene expression. However, the relationship between Ca2+ signaling and gene expression in vascular smooth muscle is not well understood. This study examines the ability of Ca2+ influx through voltage-dependent, L-type Ca2+ channels (VDCCs) and Ca2+ release through ryanodine receptors (RyRs) to activate the transcription factor, cAMP-responsive element binding protein (CREB), and increase c-fos levels in intact cerebral arteries. Membrane depolarization increased the fraction of nuclei staining for phosphorylated CREB (P-CREB) and levels of c-fos mRNA in intact mouse cerebral arteries. Ryanodine, which inhibits RyRs, increased P-CREB staining and c-fos levels. Forskolin, an activator of adenylyl cyclase, and sodium nitroprusside, an NO donor, increased P-CREB and c-fos levels. Nisoldipine, an inhibitor of VDCCs, reversed the effects of depolarization and ryanodine on P-CREB and c-fos levels, but not the effects of forskolin or sodium nitroprusside. Inhibition of Ca2+/calmodulin-dependent protein kinase (CaM kinase) blocked increases in P-CREB and c-fos levels seen with membrane depolarization, suggesting that CaM kinase has an important role in the pathway leading from Ca2+ influx to CREB-mediated changes in c-fos levels. Our data suggest that membrane depolarization increases [Ca2+], through activation of VDCCs, leading to increased P-CREB and c-fos, and that RyRs have a profound effect on this pathway by indirectly regulating Ca2+ entry through VDCCs. These results provide the first evidence of Ca2+ regulation of CREB and c-fos in arterial smooth muscle.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据