NADPH oxidase is involved in prostaglandin F2alpha-induced hypertrophy of vascular smooth muscle cells: induction of NOX1 by PGF2alpha.
Prostaglandin (PG) F(2alpha), 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 PGF(2alpha)-induced hypertrophy, the involvement of reactive oxygen species was examined in a rat vascular smooth muscle cell line, A7r5. PGF(2alpha) and (+)-fluprostenol, a selective agonist of the PGF receptor, significantly increased intracellular O(2)(-) in A7r5. The PGF(2alpha)-induced O(2)(-) increase was suppressed by diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase that has been reported to be the major source of O(2)(-) in vascular cells. The augmented synthesis of the protein induced by PGF(2alpha) or (+)-fluprostenol was suppressed in the presence of DPI. In PGF(2alpha) or (+)-fluprostenol-treated cells, a dose-dependent increase in the expression of NOX1, a homolog of the catalytic subunit of the phagocyte NADPH oxidase gp91(phox), 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 PGF(2alpha)-induced increase in protein synthesis. Taken together, these results suggest that hypertrophy of vascular smooth muscle cells caused by PGF(2alpha) is mediated by NOX1 induction and the resultant overproduction of O(2)(-) by NADPH oxidase.
Katsuyama
Masato
M
Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Fan
ChunYuan
C
Yabe-Nishimura
Chihiro
C
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000378:metabolism; D015237:Dinoprost / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D006984:Hypertrophy; D008024:Ligands; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology*; D019255:NADPH Oxidases / Q000737:chemistry / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D010587:Phagocytosis; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D016337:RNA, Catalytic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D018076:DNA, Complementary; D008024:Ligands; D016337:RNA, Catalytic; D012333:RNA, Messenger; D015237:Dinoprost; D019255:NADPH Oxidases