Document Detail


Thioredoxin system in cell death progression.
MedLine Citation:
PMID:  22530689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SIGNIFICANCE: The thioredoxin (Trx) system, comprising nicotinamide adenine dinucleotide phosphate, Trx reductase (TrxR), and Trx, is critical for maintaining cellular redox balance and antioxidant function, including control of oxidative stress and cell death.
RECENT ADVANCES: Here, we focus on the research progress that is involved in the regulation of apoptosis by Trx systems. In mammalian cells, cytosolic Trx1 and mitochondrial Trx2 systems are the major disulfide reductases supplying electrons to enzymes for cell proliferation and viability. The reduced/dithiol form of Trxs binds to apoptosis signal-regulating kinase 1 (ASK1) and inhibits its activity to prevent stress- and cytokine-induced apoptosis. When Trx is oxidized, it dissociates from ASK1 and apoptosis is stimulated. The binding of Trx by its inhibitor Trx interacting protein (TXNIP) also contributes to the apoptosis process by removing Trx from ASK1. TrxRs are large homodimeric selenoproteins with an overall structure which is similar to that of glutathione reductase, and contain an active site GCUG in the C-terminus.
CRITICAL ISSUES AND FUTURE DIRECTIONS: In the regulation of cell death processes, Trx redox state and TrxR activities are key factors that determine the cell fate. The high reactivity of Sec in TrxRs and its accessible location make TrxR enzymes emerge as targets for pharmaceutic drugs. TrxR inactivation by covalent modification does not only change the redox state and activity of Trx, but may also convert TrxR into a reactive oxygen species generator. Numerous electrophilic compounds including some environmental toxins and pharmaceutical drugs inhibit TrxR. We have classified these compounds into four types and propose some useful principles to understand the reaction mechanism of the TrxR inhibition by these compounds.
Authors:
Jun Lu; Arne Holmgren
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-06-11
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  17     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-03-12     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1738-47     Citation Subset:  IM    
Affiliation:
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / genetics,  physiology*
Humans
Oxidation-Reduction
Thioredoxin-Disulfide Reductase / genetics,  metabolism
Thioredoxins / genetics,  metabolism*
Chemical
Reg. No./Substance:
52500-60-4/Thioredoxins; EC 1.8.1.9/Thioredoxin-Disulfide Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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