Mechanisms of angiotensin II-induced ERK1/2 activation in fetal cardiomyocytes

Abstract

Fetal cardiomyocytes have been utilized in studies on myocardial repair in the damaged hearts of rodents and other species. Changes in angiotensin II (Ang II) receptor expression, especially decline of its type II receptor (AT2), are known to occur during the growth of cardiomyocytes from fetus to adult. However, the extent to which changes in the signaling pathways of Ang II type I (AT1) and AT2 receptors via p42/44 mitogen-activated protein kinase (ERK1/2) activation affect the physiological and pathophysiological functions in cardiomyocytes has not been defined. The roles of these receptors were analyzed by confocal fluorescence microscopy, immunoblot analysis, reverse transcription PCR, measurement of intracellular 3',5'-cyclic AMP levels and siRNA technology in cultured rat fetal cardiomyocytes. These studies revealed that Gq is required for Ang II-induced ERK1/2 activation via the synergy of AT1 and AT2 receptors. It has also been shown that phospholipase Cβ1, protein kinase Cα and protein kinase A mediate the feedback inhibition of ERK1/2 activation via c-Raf and/or other intermediate signaling molecules. The observed mechanism of Ang II-induced ERK1/2 activation in fetal cardiomyocytes could be relevant to the understanding of cardiomyocyte development and turnover, as well as clinical approaches using protein- and cell-based therapy for diseases such as heart failure.