NADPH oxidase is involved in prostaglandin F2α-induced hypertrophy of vascular smooth muscle cells. Induction of NOX1 by PGF2α

Abstract

Prostaglandin (PG) F2α, one of the primary prostanoids generated in vascular tissue, is known to cause hypertrophy in vascular smooth muscle cells. To clarify the molecular mechanisms underlying PGF2α-induced hypertrophy, the involvement of reactive oxygen species was examined in a rat vascular smooth muscle cell line, A7r5. PGF2α and (+)-fluprostenol, a selective agonist of the PGF receptor, significantly increased intracellular O2- in A7r5. The PGF2α-induced O2- increase was suppressed by diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase that has been reported to be the major source of O2- in vascular cells. The augmented synthesis of the protein induced by PGF2α or (+)-fluprostenol was suppressed in the presence of DPI. In PGF2α or (+)-fluprostenol-treated cells, a dose-dependent increase in the expression of NOX1, a homolog of the catalytic subunit of the phagocyte NADPH oxidase gp91phox, was demonstrated by Northern blot analysis. Finally, depletion of NOX1 mRNA in the cells transfected with ribozymes targeted for three independent cleavage sites on the mRNA sequence significantly reduced the PGF2α-induced increase in protein synthesis. Taken together, these results suggest that hypertrophy of vascular smooth muscle cells caused by PGF2α is mediated by NOX1 induction and the resultant overproduction of O2- by NADPH oxidase.