Reactive Oxygen Species Modulate Angiotensin II-Induced β-Myosin Heavy Chain Gene Expression via Ras/Raf/Extracellular Signal-Regulated Kinase Pathway in Neonatal Rat Cardiomyocytes

Abstract

Angiotensin II (Ang II) causes cardiomyocytes hypertrophy. Cardiac β-myosin heavy chain (β-MyHC) gene expression can be altered by Ang II. The molecular mechanisms are not completely known. Reactive oxygen species (ROS) are involved in signal transduction pathways of Ang II. However, the role of ROS on Ang II-induced β-MyHC gene expression remains unclear. Here we found that Ang II increased β-MyHC promoter activity and it was blocked by Ang II type 1 receptor antagonist losartan. Ang II dose-dependently increased the intracellular ROS. Cardiomyocytes cotransfected with a dominant negative mutant of Ras (RasN17), Raf-1 (Raf301), or a catalytically inactive mutant of extracellular signal regulated kinase (mERK2) inhibited Ang II-induced β-MyHC promoter activity, indicating Ras/Raf/ERK pathway was involved. Antioxidants such as catalase or N-acetyl-cysteine decreased Ang II-activated ERK phosphorylation and inhibited Ang II-induced β-MyHC promoter activity. These data indicate that Ang II increases β-MyHC gene expression in part via the generation of ROS.