Superoxide anion-induced formation of inositol phosphates involves tyrosine kinase activation in smooth muscle cells from rat mesenteric artery.
Our previous studies have demonstrated an enhanced production of inositol phosphates (IPs) induced by superoxide in smooth muscle cells (SMCs). The mechanisms for this effect, however, remained largely unknown. In the present study, it was found that superoxide increased IP production in SMCs from rat mesenteric arteries in a time-dependent manner. The effect of superoxide on IP formation was significantly inhibited by the antioxidants n-acetylcysteine or alpha-lipoic acid. Genistein and tyrphostin A25, two tyrosine kinase inhibitors, also inhibited the superoxide-induced IP formation. The application of monoclonal antibody against phospholipase Cgamma (PLCgamma) significantly inhibited the superoxide-induced IP formation. Finally, the expression level of PLCgamma proteins was increased 6 hrs after exposing SMCs to superoxide. The present findings demonstrate that superoxide activates the tyrosine kinase pathway and suggest that the tyrosine kinase-mediated IP formation may represent a novel mechanism underlying the signalling role of superoxide in rat mesenteric artery SMCs.
Wu
L
L
Groupe de recherche sur le système nerveux autonome, Faculté de Médicine, Université de Montréal, Succursale Centre-ville, Montréal, Québec, H3C 3J7, Canada.
de Champlain
J
J
D000111:Acetylcysteine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007527:Isoenzymes / Q000378:metabolism; D008638:Mesenteric Arteries / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D051966:Phospholipase C gamma; D014176:Protein Biosynthesis / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013481:Superoxides / Q000494:pharmacology*; D008063:Thioctic Acid / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D007527:Isoenzymes; D020032:Tyrphostins; D013481:Superoxides; D000804:Angiotensin II; C079836:tyrphostin 25; D008063:Thioctic Acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D000111:Acetylcysteine