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Peng, X.* ; Mandal, P.K. ; Kaminskyy, V.O.* ; Lindqvist, A.* ; Conrad, M. ; Arner, E.S.J.*

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

Cell Death Dis. 5:e1235 (2014)
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Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Glucose ; Mouse Embryonic Fibroblasts (mefs) ; Reactive Oxygen Species (ros) ; Selenocysteine ; Thioredoxin Reductase 1 (trxr1); Thioredoxin Reductase 1; Reactive Oxygen; Mammalian Thioredoxin; Hydrogen-peroxide; Diabetic Complications; Dna-replication; Stem-cells; Glutathione; Death; Apoptosis
ISSN (print) / ISBN 2041-4889
e-ISSN 2041-4889
Quellenangaben Volume: 5, Issue: , Pages: , Article Number: e1235 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed