Uncoupling Endothelial Nitric Oxide Synthase Is Ameliorated by Green Tea in Experimental Diabetes by Re-establishing Tetrahydrobiopterin Levels

Autor(es)

Faria, Aline M. ^[1] ; Papadirnitriou, Alexandros ^[1] ; Silva, Kamila C. ^[1] ; Lopes de Faria, Jacqueline M. ^[1] ; Lopes de Faria, Jose B. ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas Unicamp, Fac Med Sci, Renal Pathophysiol Lab, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Diabetes; v. 61, n. 7, p. 1838-1847, JUL 2012.
• Citações Web of Science: 38

Resumo

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 (BH4) 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. BH4 and the activity of guanosine triphosphate cyclohydrolase I decreased in ihMCs exposed to HG and was normalized by GT. Exogenous administration of BH4 in ihMCs reversed the HG-induced rise in ROS and the decline in NO production. However, coadministration of GT with BH4 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 BH4 levels, ameliorating uncoupling eNOS, and thus increasing NO bioavailability and reducing oxidative stress, two abnormalities that are involved in the pathogenesis of diabetic nephropathy. Diabetes 61:1838-1847, 2012 (AU)

• Processo FAPESP: 08/57560-0 - Efeitos do chá verde (Camellia sinensis), do cacau e de um doador de óxido nítrico na nefropatia e retinopatia diabética: papel da redução do estresse oxidativo e da inflamação e do aumento do óxido nítrico
• Beneficiário: Jose Butori Lopes de Faria
• Modalidade de apoio: Auxílio à Pesquisa - Temático