Document Detail

Short-interfering RNA-mediated silencing of thioredoxin reductase 1 alters the sensitivity of HeLa cells toward cadmium.
MedLine Citation:
PMID:  16508163     Owner:  NLM     Status:  MEDLINE    
The mammalian thioredoxin reductase (TrxR) is a selenocysteine-containing flavoprotein that regulates the thioredoxin system, one of the major systems that maintain the intracellular redox balance. We previously reported that cytosolic TrxR (TrxR1), one of three mammalian TrxR isozymes, was induced by treatment with cadmium. In the present study, to study the role of cadmium-induced TrxR1 in cellular defense, we silenced the expression of TrxR1 in HeLa cells by using small interfering RNA and examined the effect of TrxR1 silencing on the sensitivity of the cells toward cadmium. We found that the gene silencing of TrxR1 had a dual effect on cadmium-induced cell death, depending on the concentration of cadmium. The TrxR1 silencing increased the sensitivity toward a low dose (less than 10 microM) of cadmium but decreased the sensitivity toward a high dose of cadmium. These results suggested that TrxR1 might play an important role in the cellular defense system against cadmium in two ways. TrxR1 might rescue the cells from a low dose of cadmium-induced moderate injury, while it might promote the death of cells severely injured by a high dose of cadmium.
Michie Nishimoto; Motoharu Sakaue; Shuntaro Hara
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  29     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-01     Completed Date:  2006-05-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  543-6     Citation Subset:  IM    
Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
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MeSH Terms
Arsenic Poisoning / enzymology,  genetics,  pathology
Blotting, Northern
Cadmium Poisoning / enzymology*,  genetics*,  pathology
Cell Death / drug effects
Gene Silencing
Hela Cells
Hydrogen Peroxide / toxicity
Mercury Poisoning / enzymology,  genetics,  pathology
Oxidants / toxicity
RNA, Small Interfering / pharmacology*
Tetrazolium Salts
Thioredoxin Reductase 1
Thioredoxin-Disulfide Reductase / biosynthesis,  genetics*
Reg. No./Substance:
0/Oxidants; 0/RNA, Small Interfering; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 7722-84-1/Hydrogen Peroxide; EC protein, human; EC Reductase 1; EC Reductase

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