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Extracellular alkalosis activates ERK mitogen-activated protein kinase of vascular smooth muscle cells through NADPH-mediated formation of reactive oxygen species.

Abstract
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.
AuthorsShinji Susa, Ichiro Wakabayashi
JournalFEBS letters (FEBS Lett) Vol. 554 Issue 3 Pg. 399-402 (Nov 20 2003) ISSN: 0014-5793 [Print] England
PMID14623101 (Publication Type: Journal Article)
Chemical References
  • Onium Compounds
  • Reactive Oxygen Species
  • 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
  • NADP
  • Superoxide Dismutase
  • NADPH Oxidases
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate
  • HEPES
  • Calcium
Topics
  • 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt (pharmacology)
  • Animals
  • Aorta (cytology)
  • Calcium (chemistry, metabolism)
  • Enzyme Activation
  • HEPES (pharmacology)
  • Hydrogen-Ion Concentration
  • Male
  • Mitogen-Activated Protein Kinases (metabolism)
  • Muscle, Smooth, Vascular (cytology, metabolism)
  • NADP (metabolism)
  • NADPH Oxidases (antagonists & inhibitors, metabolism)
  • Onium Compounds (pharmacology)
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species (antagonists & inhibitors, metabolism)
  • Superoxide Dismutase (metabolism, pharmacology)
  • Tetradecanoylphorbol Acetate (pharmacology)

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