title: Uncoupling endothelial nitric oxide synthase is ameliorated by green tea in experimental diabetes by re-establishing tetrahydrobiopterin levels.
abstract: The current study investigated the potential of green tea (GT) to improve uncoupling of endothelial nitric oxide synthase (eNOS) in diabetic conditions. In rats with streptozotocin-induced diabetes, nitric oxide (NO) bioavailability was reduced by uncoupling eNOS, characterized by a reduction in tetrahydrobiopterin (BH(4)) levels and a decrease in the eNOS dimer-to-monomer ratio. GT treatment ameliorated these abnormalities. Moreover, immortalized human mesangial cells (ihMCs) exposed to high glucose (HG) levels exhibited a rise in reactive oxygen species (ROS) and a decline in NO levels, which were reversed with GT. BH(4) and the activity of guanosine triphosphate cyclohydrolase I decreased in ihMCs exposed to HG and was normalized by GT. Exogenous administration of BH(4) in ihMCs reversed the HG-induced rise in ROS and the decline in NO production. However, coadministration of GT with BH(4) did not result in a further reduction in ROS production, suggesting that reduced ROS with GT was indeed secondary to uncoupled eNOS. In summary, GT reversed the diabetes-induced reduction of BH(4) levels, ameliorating uncoupling eNOS, and thus increasing NO bioavailability and reducing oxidative stress, two abnormalities that are involved in the pathogenesis of diabetic nephropathy.
authors.affiliation: Renal Pathophysiology Laboratory, Investigation on Diabetes Complications, Faculty of Medical Sciences, State University of Campinas,Campinas, São Paulo, Brazil. jblfaria@fcm.unicamp.br
authors.forename: Aline M
authors.initials: AM
authors.lastname: Faria
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: Kamila C
authors.initials: KC
authors.lastname: Silva
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lopes de Faria
authors.forename: José B
authors.initials: JB
authors.lastname: Lopes de Faria
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D028241:Camellia sinensis; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D006136:GTP Cyclohydrolase / Q000378:metabolism; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000032:analysis; D013662:Tea
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013662:Tea; D001708:Biopterins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006136:GTP Cyclohydrolase; C003402:sapropterin