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首页> 外文期刊>Journal of Cellular Physiology >Regulation of angiotensin II-stimulated osteopontin expression in cardiac microvascular endothelial cells: role of p42/44 mitogen-activated protein kinase and reactive oxygen species.
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Regulation of angiotensin II-stimulated osteopontin expression in cardiac microvascular endothelial cells: role of p42/44 mitogen-activated protein kinase and reactive oxygen species.

机译:调节血管紧张素II-stimulated骨桥蛋白表达在心脏微血管内皮细胞:p42/44的角色增殖蛋白激酶活性氧物种。

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Using spontaneously hypertensive and aortic banded rats, we have shown that expression of myocardial osteopontin, an extracellular matrix protein, coincides with the development of heart failure and is inhibited by captopril, suggesting a role for angiotensin II (ANG II). This study tested whether ANG II induces osteopontin expression in adult rat ventricular myocytes and cardiac microvascular endothelial cells (CMEC), and if so, whether induction is mediated via activation of mitogen-activated protein kinases (p42/44 MAPK) and involves reactive oxygen species (ROS). ANG II (1 &mgr;M, 16 h) increased osteopontin expression (fold increase 3.3+/-0.34, n = 12, P < 0.01) in CMEC as measured by northern analysis, but not in ARVM. ANG II stimulated osteopontin expression in CMEC in a time- (within 4 h) and concentration-dependent manner, which was prevented by the AT1 receptor antagonist, losartan. ANG II elicited robust phosphorylation of p42/44 MAPK as measured using phospho-specific antibodies, and increased superoxide production as measured by cytochrome c reduction and lucigenin chemiluminescence assays. These effects were blocked by diphenylene iodonium (DPI), an inhibitor of the flavoprotein component of NAD(P)H oxidase. PD98059, an inhibitor of p42/44 MAPK pathway, and DPI each inhibited ANG II-stimulated osteopontin expression. Northern blot analysis showed basal expression of p22phox, a critical component of NADH/NADPH oxidase system, which was increased 40-60% by exposure to ANG II. These results suggest that p42/44 MAPK is a critical component of the ROS-sensitive signaling pathways activated by ANG II in CMEC and plays a key role in the regulation of osteopontin gene expression. Published 2001 Wiley-Liss, Inc.
机译:使用自发性高血压和主动脉带状老鼠,我们已经表明,心肌的表情骨桥蛋白、细胞外基质蛋白恰逢心力衰竭的发展由卡托普利抑制,表明一个角色血管紧张素ⅱ(ANG II)。本研究测试是否和II诱导骨桥蛋白表达成年大鼠心室细胞和心脏机械设备进出口总公司的微血管内皮细胞(),如果所以,无论感应是通过激活介导的增殖作用的蛋白激酶(p42/44MAPK),包括活性氧(ROS)。表达式(褶皱增加3.3 + / - -0.34,n = 12, P <机械设备进出口总公司的0.01)在北部的分析,但不是在ARVM。机械设备进出口总公司的表达在一个时间(4小时内)和浓度的方式,预防AT1受体拮抗剂,洛沙坦。使用phospho-specific的p42/44 MAPK来衡量抗体,增加超氧化物生产以细胞色素c还原和衡量lucigenin化学发光检测。被封锁的二苯基碘鎓(DPI),一个黄素蛋白的抑制剂的组成部分NAD (P) H氧化酶。每个抑制MAPK通路,DPI和II-stimulated骨桥蛋白表达。污点分析显示基底的p22phox的表达,NADH / NADPH氧化酶的一个关键组成部分系统,它被暴露在增加了40 - 60%ANG II。ROS-sensitive的一个关键组成部分机械设备进出口总公司的ANGⅱ在信号通路激活和调节起着关键作用骨桥蛋白基因表达。Wiley-Liss公司。

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