Document Detail


Thiophosphate and selenite conversely modulate cell death induced by glutathione depletion or cisplatin - effects related to activity and Sec contents of thioredoxin reductase.
MedLine Citation:
PMID:  22784015     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Thiophosphate (SPO3) was recently shown to promote Cys insertion at Sec-encoding UGA codons during selenoprotein synthesis. We earlier reported that irreversible targeting by cisplatin (cDDP) of the Sec residue in thioredoxin reductase 1 (TrxR1) contributes to cDDP cytotoxicity. This effect could possibly be attenuated in cells expressing less reactive Sec-to-Cys substituted TrxR1 variants, or pronounced in cells with higher levels of Sec-containing TrxR1. To test this, we here supplemented cells with either SPO3 or selenium and subsequently determined total as well as specific activities of cellular TrxR1, together with extent of drug-induced cell death. We found that cDDP became less cytotoxic after incubation of A549 or HCT116 cells with lower SPO3 concentrations (100 mM - 300 mM), while higher SPO3 (<300 µM) had pronounced direct cytotoxicity. NIH 3T3 cells showed low basal TrxR1 activity and high susceptibility to SPO3 cytotoxicity, or to glutathione depletion. Supplementing NIH 3T3 cells with selenite, however, gave increased cellular TrxR1 activity with concomitantly decreased dependence upon glutathione, while the susceptibility to cDDP increased. The results suggest molecular mechanisms by which the selenium status of cells can affect their glutathione dependence while modulating the cytotoxicity of drugs that target TrxR1.
Authors:
Xiaoxiao Peng; Jianqiang Xu; Elias S J Arnér
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-11
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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