Reactive oxygen species modulate angiotensin II-induced beta-myosin heavy chain gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in neonatal rat cardiomyocytes

Angiotensin II (Ang II) causes cardiomyocytes hypertrophy, Cardiac beta -my osin heavy chain (beta -MyHC) gene expression can be altered by Ang II. The molecular mechanisms are not completely known. Reactive oxygen species (RO S) are involved in signal transduction pathways of Ang II. However, the rol e of ROS on Ang II-induced beta -MyHC gene expression remains unclear. Here we found that Ang II increased beta -MyHC promoter activity and it was blo cked by Ang II type 1 receptor antagonist losartan. Ang II dose-dependently increased the intracellular ROS. Cardiomyocytes cotransfected with a domin ant negative mutant of Ras (RasN17), Raf-1 (Raf301), or a catalytically ina ctive mutant of extracellular signal regulated kinase (mERK2) inhibited Ang II-induced beta -MyHC promoter activity, indicating Ras/Raf/ERK pathway wa s involved. Antioxidants such as catalase or N-acetylcysteine decreased Ang II-activated ERK phosphorylation and inhibited Ang II-induced beta -MyHC p romoter activity. These data indicate that Ang II increases beta -MyHC gene expression in part via the generation of ROS. (C) 2001 Academic Press.