N-acetylcysteine inhibits angiotensin II-mediated activation of extracellular signal-regulated kinase and epidermal growth factor receptor

Angiotensin II (Ang II) is known to stimulate reactive oxygen species (ROS) generation and epidermal growth factor (EGF) receptor transactivation to m ediate growth-promoting signals such as extracellular signal-regulated kina se (ERK) in vascular smooth muscle cells (VSMCs). However, how ROS and EGF receptor interact to orchestrate these signals in VSMCs remains unclear. Me re we found that an antioxidant, N-acetylcysteine, inhibited ERK activation and EGF receptor tyrosine phosphorylation induced by Ang II. Moreover, H2O 2 stimulates EGF receptor tyrosine phosphorylation and EGF receptor inhibit ors attenuated H2O2-induced ERK activation. These data indicate that ROS me diate Ang II-induced EGF receptor transactivation, a critical mechanism for ERK-dependent growth in VSMCs. (C) zool Academic Press.