کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2019968 | 1542255 | 2006 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Oxidative alterations of cyclooxygenase during atherogenesis
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Nitric oxide (NO) and eicosanoids are critical mediators of physiological and pathophysiological processes. They include inflammation and atherosclerosis. NO production and eicosanoid synthesis become disrupted during atherosclerosis and thus, it is important to understand the mechanisms that may contribute to this outcome. We, and others, have shown that nitrogen oxide (NOx) species modulate cyclooxygenase (COX; also known as prostaglandin H2 synthase) activity and alter eicosanoid production. We have determined that peroxynitrite (ONOOâ) has multiple effects on COX activity. ONOOâ can provide the peroxide tone necessary for COX activation, such that simultaneous exposure of COX to its arachidonic acid substrate and ONOOâ results in increased eicosanoid production. Alternatively, in the absence of arachidonic acid, ONOOâ can modify COX through nitration of an essential tyrosine residue (Tyr385) such that it is incapable of catalysis. In this regard, we have shown that COX nitration occurs in human atherosclerotic tissue and in aortic lesions from ApoEâ/â mice kept on a high fat diet. Additionally, we have demonstrated that Tyr nitration in ApoEâ/â mice is dependent on the inducible form of NO synthase (iNOS). Under conditions where ONOOâ persists and arachidonic acid is not immediately available, the cell may try to correct the situation by responding to ONOOâ and releasing arachidonic acid via a signaling pathway to favor COX activation. Other post-translational modifications of COX by NOx species include S-nitrosation of cysteine (Cys) residues (which may have an activating effect) and Cys oxidation. The central focus of this review will include a discussion of how NOx species alter COX activity at the molecular level and how these modifications may contribute to altered eicosanoid output during atherosclerosis and lesion development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Prostaglandins & Other Lipid Mediators - Volume 80, Issues 1â2, July 2006, Pages 1-14
Journal: Prostaglandins & Other Lipid Mediators - Volume 80, Issues 1â2, July 2006, Pages 1-14
نویسندگان
Rita K. Upmacis, Ruba S. Deeb, David P. Hajjar,