title: Piceatannol is more effective than resveratrol in restoring endothelial cell dimethylarginine dimethylaminohydrolase expression and activity after high-glucose oxidative stress.
abstract: 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.
authors.affiliation: 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. matthieu.frombaum@etu.parisdescartes.fr
authors.forename: Matthieu
authors.initials: M
authors.lastname: Frombaum
authors.forename: Patrice
authors.initials: P
authors.lastname: Therond
authors.forename: Raja
authors.initials: R
authors.lastname: Djelidi
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Beaudeux
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: Didier
authors.initials: D
authors.lastname: Borderie
mesh_terms: D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015153:Blotting, Western; D002417:Cattle; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy; D047468:Immunoprecipitation; D009281:Naphthalenes / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011753:Pyrones / Q000494:pharmacology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D009281:Naphthalenes; D011753:Pyrones; D013267:Stilbenes; C487735:dimethylarginine; C444426:splitomicin; C041525:3,3',4,5'-tetrahydroxystilbene; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; D056564:Sirtuin 1; D001119:Arginase; C059999:dimethylargininase; D005947:Glucose; D000077185:Resveratrol