کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10738398 1046704 2011 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Alleviation of oxidative stress by potent and selective thioredoxin-mimetic peptides
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Alleviation of oxidative stress by potent and selective thioredoxin-mimetic peptides
چکیده انگلیسی
One of the major enzymatic cell defenses providing protection from oxidative injury is the TrxR-Trx system. It consists of NADPH and thioredoxin reductase (TrxR), which maintain thioredoxin (Trx) in a reduced state. Perturbing the TrxR-Trx system with the selective TrxR inhibitor auranofin (AuF; 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranosato-S-(triethylphosphine) gold) induces oxidative stress by keeping Trx in its oxidized state. We have prepared a family of tri- and tetra-oligopeptides derived from the canonical CxxC motif of the Trx active site and a modified CxC motif. These Trx-mimetic compounds are N- and C-terminal-blocked peptides that consist of two cysteine residues that flank the two-amino-acid CxxC motif (CB4 and CB6) or the single-amino-acid CxC motif (CB3). Catecholamine (CA) secretion in bovine chromaffin cells, which is a highly redox sensitive process, is abolished by AuF. The Trx-mimetic peptides effectively restore CA secretion, as monitored by amperometry in single cells. They also prevent the AuF-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase. In PC12 cells, the alleviation of AuF-induced ERK1/2-MAPK phosphorylation by Trx-like peptides parallels their effect of restoring CA secretion. CB3, CB4, and CB6 act intracellularly and are significantly more potent than the traditional antioxidants NAC, GSH, DTT, AD4 (NAC-amide), and ascorbic acid. Taken together, the CxxC and CxC peptides represent a new family of potent and selective redox compounds that could serve as potential candidates for prevention and treatment of oxidative-stress-related disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 50, Issue 10, 15 May 2011, Pages 1355-1367
نویسندگان
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