期刊
CIRCULATION
卷 105, 期 18, 页码 2206-2211出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000015602.94990.3D
关键词
hypoxia; nitric oxide; proteins; growth substances
Background-Reoxygenation injury is a result of several complex events, including release of reactive oxygen species, protein kinase C (PKC) activation, and altered expression of transforming growth factor-beta(1) (TGF-beta(1)). Nitric oxide (NO) generally protects tissues from reperfusion injury. Methods and Results-We examined the modulation of TGF-beta(1) expression and activity and PKC activation in cultured rat heart myocytes exposed to a brief period of hypoxia-reoxygenation (H-R) by NO donor 3-morpholino-sydnonimine (SIN-1). H-R resulted in an increased expression of total TGF-beta(1) (mRNA and protein) but a decrease in the release of active TGF-beta(1). Myocyte PKC-alpha protein level was not altered by H-R, but its phosphorylation was augmented. Pretreatment of myocytes with SIN-1 diminished myocyte injury quantified as lactate dehydrogenase release. Simultaneously, release of active TGF-beta(1) increased and total TGF-beta(1) expression decreased (all P<0.05 versus H-R alone). PKC-alpha phosphorylation increased further in cells treated with SIN-1. The effects of SIN-1 were blocked by the NO scavenger phenyl-tetramethyl-imidazoline-oxyl-oxide as well as by the PKC inhibitor staurosporine. To examine if another NO donor would have a similar effect, cardiomyocytes were treated with nitroglycerin before H-R. With nitroglycerin treatment, similar to SIN-1 treatment, myocyte injury was diminished, TGF-beta(1) release increased, and total TGF-beta(1) expression decreased. Conclusions-These observations suggest modulation of TGF-beta(1) expression as a novel mechanism of salutary effect of NO donors. PKC-alpha activation may play an important role in the protective effect of NO against H-R injury.
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