کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1910769 1046786 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of peroxynitrite in endothelial damage mediated by Cyclosporine A
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Role of peroxynitrite in endothelial damage mediated by Cyclosporine A
چکیده انگلیسی
Although Cyclosporine A (CsA) is an effective therapy for immunosuppression, its use encompasses serious side effects that have been associated with oxidative stress. We previously reported the intracellular formation of both peroxynitrite and 3-nitrotyrosine in cultured bovine aortic endothelial cells (BAEC) when exposed to CsA. Here we show that re-addition of CsA to BAEC increases peroxynitrite formation in a concentration-dependent manner. This effect is inhibited by the glutathione donor and antioxidant, N-acetylcysteine (NAC). BAEC exposed to CsA showed impaired integrity of plasma membranes and increased cytolysis, a phenomenon prevented by NAC. When CsA was administered to mice, the increased presence of 3-nitrotyrosine was detected in the aortic endothelium, an effect also abrogated by the concomitant administration of NAC. An increase in nitrated MnSOD was detected in BAEC treated with CsA and the peroxynitrite donor SIN-1 and recapitulated in recombinant MnSOD, exposed to the conditioned media from BAEC. We propose that CsA promotes nitration of specific molecular targets, such as MnSOD, within vascular endothelial cells. This may represent a pathogenetic mechanism of vascular injury. Inhibition of this process by clinically applicable antioxidants, such as NAC, lends a basis for the exploration of therapeutic alternatives in patients treated with CsA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 42, Issue 3, 1 February 2007, Pages 394-403
نویسندگان
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