These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: PRMT-1 and DDAHs-induced ADMA upregulation is involved in ROS- and RAS-mediated diabetic retinopathy.
    Author: Chen Y, Xu X, Sheng M, Zhang X, Gu Q, Zheng Z.
    Journal: Exp Eye Res; 2009 Dec; 89(6):1028-34. PubMed ID: 19748504.
    Abstract:
    Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is generated in presence of type 1 protein arginine N-methyltransferase (PRMT-1) and is metabolized by dimethylarginine dimethylaminohydrolases (DDAHs). Reportedly ADMA is associated with endothelial dysfunction. The aim of this study is to investigate whether PRMT-1- and DDAHs-induced ADMA increase in diabetic rat retina and high glucose-treated bovine retinal capillary endothelial cells (BRCECs) is involved in reactive oxygen species (ROS)- and renin-angiotensin system (RAS)-mediated diabetic retinopathy. Rats were divided into four groups: sham-injected group, streptozotocin (STZ)-induced diabetic model group, STZ-induced diabetic model plus 12-week ACEI benazepril treatment group, and STZ-induced diabetic model plus 12-week ARB telmisartan treatment group. BRCECs were exposed to 5mM glucose, 30mM glucose, and 30mM glucose plus benazepril, telmisartan, diphenyliodonium (NADPH oxidase inhibitor, DPI), or N-Acetyl-l-cysteine (antioxidant and free radical scavenger, NAC) until passage four. We found that the concentrations of ADMA were significantly elevated in the plasma of diabetic rat models, and were significantly reduced by benazepril or telmisartan. DDAHs expression was decreased and PRMT-1 expression was increased in diabetic rat retina, which was reversed by benazepril. Telmisartan decreased PRMT-1 expression and increased DDAH II expression, but had no effect on DDAH I expression. In vitro, BRCECs exposed to high glucose had elevated ROS production, decreased cGMP, increased PRMT-1 expression, and decreased DDAH activity and DDAH II expression. Coincubating BRCECs with benazepril, telmisartan, DPI or NAC reversed the effects of high glucose. It can be concluded that PRMT-I and DDAHs-induced upregulation of ADMA levels might be involved in ROS- and RAS-mediated diabetic retinopathy.
    [Abstract] [Full Text] [Related] [New Search]