EA 4466 Stress Cellulaire, Physiopathologie, stratégies nutritionnelles et thérapeutiques innovantes, Université Paris Descartes, UFR des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75006 Paris, France.
Free Radic Res. 2011 Mar;45(3):293-302. doi: 10.3109/10715762.2010.527337. Epub 2011 Jan 14.
Glucose-induced oxidative stress is involved in endothelial dysfunction. Dimethylarginine dimethylaminohydrolase (DDAH) and arginase are regulators of the endothelial NO synthase (eNOS). This study aimed to compare the effect of two polyphenolic antioxidants, resveratrol and piceatannol, on DDAH and arginase pathways in bovine aortic endothelial cells under 25 mM glucose for 24 h. DDAH activity and expression were decreased in these cells as compared to control cells, whereas arginase activity was unchanged. DDAH inhibition led to intracellular accumulation of asymmetric dimethylarginine (ADMA), a natural inhibitor of eNOS. Under these conditions, cell pre-treatment with resveratrol (0.1-10 μM) restored basal DDAH activity and ADMA level with a dose-dependent effect. Piceatannol acted as resveratrol on DDAH pathway but at 10-fold lower concentrations. Resveratrol and piceatannol restored DDAH activity even in the presence of splitomicin, a specific inhibitor of Sirtuin 1. These results suggest potential therapeutic intervention targeting resveratrol or piceatannol administration to improve endothelial dysfunction.
葡萄糖诱导的氧化应激参与内皮功能障碍。二甲基精氨酸二甲胺水解酶（DDAH）和精氨酸酶是内皮型一氧化氮合酶（eNOS）的调节因子。本研究旨在比较两种多酚抗氧化剂白藜芦醇和白皮杉醇在 25mM 葡萄糖作用 24 小时后对牛主动脉内皮细胞中 DDAH 和精氨酸酶途径的影响。与对照细胞相比，这些细胞中的 DDAH 活性和表达降低，而精氨酸酶活性不变。DDAH 抑制导致内源性 eNOS 抑制剂非对称性二甲基精氨酸（ADMA）的细胞内积累。在这些条件下，细胞用白藜芦醇（0.1-10μM）预处理可恢复基础 DDAH 活性和 ADMA 水平，呈剂量依赖性。白皮杉醇对 DDAH 途径的作用与白藜芦醇相同，但浓度低 10 倍。即使存在特异性 Sirtuin 1 抑制剂 Splitomicin，白藜芦醇和白皮杉醇也能恢复 DDAH 活性。这些结果表明，针对白藜芦醇或白皮杉醇给药的潜在治疗干预可能改善内皮功能障碍。
