The Human Thioredoxin System: Modifications and Clinical Applications
محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 14، شماره: 3
سال انتشار: 1390
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 186
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شناسه ملی سند علمی:
JR_IJBMS-14-3_001
تاریخ نمایه سازی: 3 آبان 1400
چکیده مقاله:
The thioredoxin system, comprising thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH, is one of the major cellular antioxidant systems, implicated in a large and growing number of biological functions. Trx acts as an oxidoreductase via a highly conserved dithiol/disulfide motif located in the active site ( Trp-Cys-Gly-Pro- Cys-Lys-). Different factors are involved in the regulation of Trx activity, including its expression level, localization, protein-protein interactions, post-translational modifications and some chemical inhibitors. Mammalian TrxRs are selenoproteins which have a –Cys-Val-Asn-Val-Gly-Cys- N-terminal active site, as well as a C-terminal selenium-containing active site. Besides two Cys-residues in the redox-regulatory domain of cytosolic Trx (Trx۱), human Trx۱ has three additional Cys-residues. Post-translational modifications of human Trx۱ which are involved in the regulation of its activity can happen via modification of Cys-residues including thiol oxidation, glutathionylation and S-nitrosylation or via modification of other amino acid residues such as nitration of Tyr-۴۹. Because of the numerous functions of the thioredoxin system, its inhibition (mainly happens via the targeting TrxR) can result in major cellular consequences, which are potentially pro-oxidant in nature, leading to cell death via necrosis or apoptosis if overexpression of Trx and other antioxidative enzymes can not recuperate cell response. Considering this feature, several anticancer drugs have been used which can inhibit TrxR. Elevated levels of Trx and/or TrxR have been reported in many different human malignancies, positively correlated with aggressive tumor growth and poor prognosis. Moreover, anti-oxidative and anti- apoptotic effects of Trx are reasons to study its clinical application as a drug.
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نویسندگان
Seyed Isaac Hashemy
Department of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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