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Cell Death Dis. 2014 May 22;5:e1235. doi: 10.1038/cddis.2014.209.

Sec-containing TrxR1 is essential for self-sufficiency of cells by control of glucose-derived H2O2.

Author information

1
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
2
1] Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental health, Marchioninistr. 25, 81377 Munich, Germany [2].
3
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
4
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
5
Helmholtz Zentrum München, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.

Abstract

It is commonly recognized that diabetic complications involve increased oxidative stress directly triggered by hyperglycemia. The most important cellular protective systems against such oxidative stress have yet remained unclear. Here we show that the selenoprotein thioredoxin reductase 1 (TrxR1), encoded by the Txnrd1 gene, is an essential enzyme for such protection. Individually grown Txnrd1 knockout (Txnrd1(-/-)) mouse embryonic fibroblasts (MEFs) underwent massive cell death directly linked to glucose-induced H2O2 production. This death and excessive H2O2 levels could be reverted by reconstituted expression of selenocysteine (Sec)-containing TrxR1, but not by expression of Sec-devoid variants of the enzyme. Our results show that Sec-containing TrxR1 is absolutely required for self-sufficient growth of MEFs under high-glucose conditions, owing to an essential importance of this enzyme for elimination of glucose-derived H2O2. To our knowledge, this is the first time a strict Sec-dependent function of TrxR1 has been identified as being essential for mammalian cells.

PMID:
24853413
PMCID:
PMC4047868
DOI:
10.1038/cddis.2014.209
[Indexed for MEDLINE]
Free PMC Article
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