Intracellular Reactive Oxygen Species Mediate the Linkage of Na1/K1-ATPase to Hypertrophy and Its Marker Genes in Cardiac Myocytes*

We showed before that in cardiac myocytes partial inhibition of Na1/K1-ATPase by nontoxic concentra-tions of ouabain causes hypertrophy and transcrip-tional regulations of growth-related marker genes through multiple Ca21-dependent signal pathways many of which involve Ras and p42/44 mitogen-acti-vated protein kinases. The aim of this work was to ex-plore the roles of intracellular reactive oxygen species (ROS) in these ouabain-initiated pathways. Ouabain caused a rapid generation of ROS within the myocytes that was prevented by preexposure of cells to N-acetyl-cysteine (NAC) or vitamin E. These antioxidants also blocked or attenuated the following actions of ouabain: inductions of the genes of skeletal a-actin and atrial natriuretic factor, repression of the gene of the a3-sub