Short-interfering RNA-mediated silencing of thioredoxin reductase 1 alters the sensitivity of HeLa cells toward cadmium.
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.
Nishimoto
Michie
M
Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Sakaue
Motoharu
M
Hara
Shuntaro
S
D020261:Arsenic Poisoning / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015152:Blotting, Northern; D002105:Cadmium Poisoning / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008630:Mercury Poisoning / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016877:Oxidants / Q000633:toxicity; D034741:RNA, Small Interfering / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D016877:Oxidants; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D006861:Hydrogen Peroxide; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase; C022616:thiazolyl blue