Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada.
Institute of Cardiovascular Sciences & Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Cells. 2022 Aug 11;11(16):2488. doi: 10.3390/cells11162488.
The activation of phospholipase C (PLC) is thought to have a key role in the cardiomyocyte response to several different hypertrophic agents such as norepinephrine, angiotensin II and endothelin-1. PLC activity results in the generation of diacylglycerol and inositol trisphosphate, which are downstream signal transducers for the expression of fetal genes, increased protein synthesis, and subsequent cardiomyocyte growth. In this article, we describe the signal transduction elements that regulate PLC gene expression. The discussion is focused on the norepinephrine- α-adrenoceptor signaling pathway and downstream signaling processes that mediate an upregulation of PLC isozyme gene expression. Evidence is also indicated to demonstrate that PLC activities self-regulate the expression of PLC isozymes with the suggestion that PLC activities may be part of a coordinated signaling process for the perpetuation of cardiac hypertrophy. Accordingly, from the information provided, it is plausible that specific PLC isozymes could be targeted for the mitigation of cardiac hypertrophy.
磷脂酶 C(PLC)的激活被认为在心肌细胞对多种不同的肥大剂(如去甲肾上腺素、血管紧张素 II 和内皮素-1)的反应中起关键作用。PLC 活性导致二酰基甘油和肌醇三磷酸的产生,它们是胎儿基因表达、蛋白质合成增加和随后心肌细胞生长的下游信号转导物。在本文中,我们描述了调节 PLC 基因表达的信号转导元件。讨论的重点是去甲肾上腺素-α-肾上腺素能信号通路和介导 PLC 同工酶基因表达上调的下游信号过程。还提供了证据表明 PLC 活性自我调节 PLC 同工酶的表达,表明 PLC 活性可能是心脏肥大持续的协调信号过程的一部分。因此,根据所提供的信息,可以合理地认为特定的 PLC 同工酶可能成为减轻心脏肥大的目标。