Coupling factor 6 downregulates platelet endothelial cell adhesion molecule-1 via c-Src activation and acts as a proatherogenic molecule
Coupling factor 6 downregulates platelet endothelial cell adhesion molecule-1 via c-Src activation and acts as a proatherogenic molecule
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DOI：
10.1016/j.atherosclerosis.2007.12.010
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发表时间：
2008-09-01
期刊：
影响因子：
5.3
通讯作者：
Okumura, Ken
中科院分区：
文献类型：
--
作者：
Kumagai, Akiko;Osanai, Tomohiro;Okumura, Ken
偶联因子6(CF6)是三磷酸腺苷合成酶的组成部分，可抑制前列环素和一氧化氮(NO)的产生。血小板内皮细胞黏附分子-1(PECAM-1)参与了剪切性NO的产生。为了研究CF6和PECAM-1的作用之间的联系，我们检测了CF6对PECAM-1表达和剪切介导的NO释放的影响，并与血管紧张素II(AngII)进行了比较。10(-7)M CF6或10(-7)M AngII作用于人脐静脉内皮细胞(HUVEC)和主动脉内皮细胞(HAEC)24 h可抑制PECAM-1基因和蛋白的表达。CF6或AngII在15min时激活HUVEC的c-Src，用其特异性抑制剂PP1阻断c-Src可使其恢复。ATPase抑制剂EfraPeptin通过阻断酸化来减弱CF6诱导的PECAM-1基因表达的抑制，而NADPH氧化酶抑制剂超氧化物歧化酶或载脂蛋白则阻断Angii诱导的PECAM-1的抑制。将细胞暴露在25dynes/cm(2)的切应力下30min，可促进eNOS在Ser(1177)处的磷酸化和NO的释放。CF6或AngII预处理HUVEC和HAEC 24 h后，HUVEC和HAEC中的HUVEC和HAEC中的HUVEC和Ang II的表达均减弱。这些提示CF6通过c-Src激活下调PECAM-1的表达，并可能通过抑制eNOS的磷酸化来减弱剪切诱导的NO释放。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Coupling factor 6 (CF6), a component of ATP synthase, suppresses the generation of prostacyclin and nitric oxide (NO). Platelet endothelial cell adhesion molecule-1 (PECAM-1) is involved in shear-induced NO production. To investigate the linkage between the actions of CF6 and PECAM-1, we examined the effects of CF6 on PECAM-1 expression and shear-mediated NO release, comparatively with those of angiotensin II (AngII). Treatment of human umbilical vein endothelial cells (HUVEC) and aortic endothelial cells (HAEC) with CF6 at 10(-7) M or AngII at 10(-7) M for 24 h suppressed PECAM-1 gene and protein expression. CF6 or AngII activated c-Src at 15 min in HUVEC, and blockade of c-Src with PP1, its specific inhibitor, restored them. Efrapeptin, an inhibitor of ATPase, attenuated CF6-induced suppression of PECAM-1 gene expression by blockade of acidification, whereas superoxide dismutase or apocinin, an inhibitor of NADPH oxidase, blocked AngII-induced suppression of PECAM-1. Exposure of the cells to shear stress at 25 dynes/cm(2) for 30 min enhanced phosphorylation of eNOS at Ser(1177) and NO release. Pretreatment with CF6 or AngII for 24 h attenuated them in HUVEC and HAEC. These suggest that CF6 downregulates PECAM-1 expression via c-Src activation and attenuates shear-induced NO release presumably by suppressing eNOS phosphorylation. (C) 2007 Elsevier Ireland Ltd. All rights reserved.