کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909867 1046743 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Melatonin blocks oxidative stress-induced increased asymmetric dimethylarginine
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Melatonin blocks oxidative stress-induced increased asymmetric dimethylarginine
چکیده انگلیسی

Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase, and its increase is associated with many systemic diseases. We recently found that increases in plasma and hepatic ADMA levels were associated with oxidative stress in young bile-duct-ligation (BDL) rats; these increases were prevented by melatonin therapy. Therefore, we used an in vivo BDL model and in vitro cultured hepatocytes to elucidate the protective mechanisms of melatonin against oxidative stress-induced increase in ADMA. We found that the presence of reactive oxygen species (ROS) in young rats with BDL leads to downregulation of dimethylarginine dimethyaminohydrolase (DDAH)-1 and -2 as well as DDAH activity. Melatonin prevented ADMA increases in the liver mainly by regulating DDAH-1 and -2. The expression and activity of DDAH were suppressed in vitro by superoxide and hydrogen peroxide (H2O2) in a time-dependent manner, whereas melatonin could block H2O2-induced downregulation of DDAH-2 as well as decreased DDAH activity, thereby preventing increases in hepatic ADMA. Our findings reveal a mechanistic basis of DDAH downregulation by ROS and suggest that melatonin might be a potential therapy for various diseases with elevated cellular ADMA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 49, Issue 6, 15 September 2010, Pages 1088–1098
نویسندگان
, , , , , , ,