کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911273 1046809 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-β peptide
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-β peptide
چکیده انگلیسی
The lipid peroxidation product 4-hydroxy-2-nonenal (HNE) is proposed to be a toxic factor in the pathogenesis of Alzheimer disease. The primary products of lipid peroxidation are phospholipid hydroperoxides, and degraded reactive aldehydes, such as HNE, are considered secondary peroxidation products. In this study, we investigated the role of amyloid-β peptide (Aβ) in the formation of phospholipid hydroperoxides and HNE by copper ion bound to Aβ. The Aβ1-42-Cu2+ (1:1 molar ratio) complex showed an activity to form phospholipid hydroperoxides from a phospholipid, 1-palmitoyl-2-linoleoyl phosphatidylcholine, through Cu2+ reduction in the presence of ascorbic acid. The phospholipid hydroperoxides were considered to be a racemic mixture of 9-hydroperoxide and 13-hydroperoxide of the linoleoyl residue. When Cu2+ was bound to 2 molar equivalents of Aβ1-42 (2 Aβ1-42-Cu2+), lipid peroxidation was inhibited. HNE was generated from one of the phospholipid hydroperoxides, 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH), by free Cu2+ in the presence of ascorbic acid through Cu2+ reduction and degradation of PLPC-OOH. HNE generation was markedly inhibited by equimolar concentrations of Aβ1-40 (92%) and Aβ1-42 (92%). However, Aβ1-42 binding 2 or 3 molar equivalents of Cu2+ (Aβ1-42-2Cu2+, Aβ1-42-3Cu2+) acted as a pro-oxidant to form HNE from PLPC-OOH. These findings suggest that, at moderate concentrations of copper, Aβ acts primarily as an antioxidant to prevent Cu2+-catalyzed oxidation of biomolecules, but that, in the presence of excess copper, pro-oxidant complexes of Aβ with Cu2+ are formed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 43, Issue 11, 1 December 2007, Pages 1552-1559
نویسندگان
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