Extracellular alkalosis activates ERK mitogen-activated protein kinase of vascular smooth muscle cells through NADPH-mediated formation of reactive oxygen species.
Extracellular alkalosis induced phosphorylation of extracellular signal-regulated kinase (ERK) and enhanced serum-induced ERK phosphorylation in cultured rat aortic smooth muscle cells. While extracellular alkalinization increased verapamil-sensitive (45)Ca(2+) uptake into the cells, ERK phosphorylation induced by extracellular alkalosis was not affected by verapamil. On the other hand, probes for oxidant signaling, such as superoxide dismutase, 4,5-dihydroxy-1,3-benzene-disulfonic acid, a cell-permeable antioxidant, and diphenyliodonium, a NADPH oxidase inhibitor, inhibited extracellular alkalosis-induced phosphorylation of ERK. These results suggest that activation of ERK induced by extracellular alkalosis is not dependent on transplasmalemmal Ca(2+) entry but is caused by reactive oxygen species derived from an activation of NADPH oxidase.
Susa
Shinji
S
Department of Hygiene and Preventive Medicine, Yamagata University School of Medicine, Iida-Nishi 2-2-2, Yamagata 990-9585, Japan.
Wakabayashi
Ichiro
I
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009861:Onium Compounds; D017382:Reactive Oxygen Species; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D009249:NADP; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D006531:HEPES; D002118:Calcium