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• W1990218063 abstract "Objective: To examine if adenosine prevents oxidant-induced mitochondrial dysfunction by producing nitric oxide (NO) in cardiomyocytes. Methods and results: Adenosine significantly enhanced the fluorescence of DAF-FM, a dye specific for NO, implying that adenosine induces synthesis of NO. Adenosine-induced NO production was blocked by both the nonspecific NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and N5-(1-Iminoethyl)-l-ornithine dihydrochloride (l-NIO), an inhibitor of endothelial NOS (eNOS), but not by N6-(1-Iminoethyl)-l-lysine hydrochloride (l-NIL), an inhibitor of inducible NOS (iNOS), indicating that adenosine activates eNOS. Adenosine also enhances eNOS phosphorylation and its activity. The adenosine A2 receptor antagonist 8-(3-chlorostyryl)caffeine but not the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine prevented the increase in NO production. CGS21680, an adenosine A2 receptor agonist, markedly increased NO, further supporting the involvement of A2 receptors. Adenosine-induced NO production was blocked by 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP2), a selective Src tyrosine kinase inhibitor, suggesting that Src tyrosine kinase is crucial for adenosine-induced NO production. Adenosine-induced NO production was partially reversed by both wortmannin and Akt inhibitor indicating an involvement of PI3-kinase/Akt. Pretreatment of cells with adenosine prevented H2O2-induced depolarization of mitochondrial membrane potential (ΔΨm). The protective effect was blocked by l-NAME and l-NIO but not by l-NIL, indicating that eNOS plays a role in the action of adenosine. The protective effect of adenosine was further suppressed by KT5823, a specific inhibitor of protein kinase G (PKG), indicating the PKG may serve as a downstream target of adenosine. Conclusion: Adenosine protects mitochondria from oxidant damage through a pathway involving A2 receptors, eNOS, NO, PI3-kinase/Akt, and Src tyrosine kinase." @default.
• W1990218063 created "2016-06-24" @default.
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• W1990218063 date "2005-03-01" @default.
• W1990218063 modified "2023-10-13" @default.
• W1990218063 title "Adenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat cardiomyocytes" @default.
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• W1990218063 doi "https://doi.org/10.1016/j.cardiores.2004.12.004" @default.
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