Upregulation of Phospholipase C Gene Expression Due to Norepinephrine-Induced Hypertrophic Response

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- α₁-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.