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磷脂酶 C 在儿茶酚胺诱导的心肌蛋白合成增加中的作用。

Role of phospholipase C in catecholamine-induced increase in myocardial protein synthesis.

机构信息

Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, R2H 2A6 MB Canada.

Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E 0T6 MB, Canada.

出版信息

Can J Physiol Pharmacol. 2022 Oct 1;100(10):945-955. doi: 10.1139/cjpp-2022-0189. Epub 2022 Jun 29.

Abstract

The activation of the α-adrenoceptor-(α-AR) by norepinephrine results in the G-protein (Gqα) mediated increase in the phosphoinositide-specific phospholipase C (PLC) activity. The byproducts of PLC hydrolytic activity, namely, 1,2-diacylglycerol and inositol-1,4,5-trisphosphate, are important downstream signal transducers for increased protein synthesis in the cardiomyocyte and the subsequent hypertrophic response. In this article, evidence was outlined to demonstrate the role of cardiomyocyte PLC isozymes in the catecholamine-induced increase in protein synthesis by using a blocker of α-AR and an inhibitor of PLC. The discussion was focused on the α-AR-Gqα-PLC-mediated hypertrophic signalling pathway from the viewpoint that it may compliment the other β-AR-G protein-adenylyl cyclase signal transduction mechanisms in the early stages of cardiac hypertrophy development, but may become more relevant at the late stage of cardiac hypertrophy. From the information provided here, it is suggested that some specific PLC isozymes may potentially serve as important targets for the attenuation of cardiac hypertrophy in the vulnerable patient population at-risk for heart failure.

摘要

去甲肾上腺素激活α-肾上腺素能受体(α-AR),导致 G 蛋白(Gqα)介导的磷酯酰肌醇特异性磷酯酶 C(PLC)活性增加。PLC 水解活性的副产物,即 1,2-二酰基甘油和肌醇-1,4,5-三磷酸,是心肌细胞中蛋白质合成增加和随后的肥厚反应的重要下游信号转导物。在本文中,通过使用α-AR 阻断剂和 PLC 抑制剂,概述了证据来证明心肌细胞 PLC 同工酶在儿茶酚胺诱导的蛋白质合成增加中的作用。讨论集中在α-AR-Gqα-PLC 介导的肥厚信号通路,因为它可能补充了心脏肥厚发展早期的其他β-AR-G 蛋白-腺苷酸环化酶信号转导机制,但在心脏肥厚的晚期可能变得更为相关。根据这里提供的信息,建议某些特定的 PLC 同工酶可能潜在地作为易患心力衰竭的高危患者群体中心脏肥厚减弱的重要靶点。

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Regulation of phosphoinositide-specific phospholipase C.磷酸肌醇特异性磷脂酶C的调节
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