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http://purl.uniprot.org/citations/22144571http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22144571http://www.w3.org/2000/01/rdf-schema#comment"

Background

Excessive formation of reactive oxygen species contributes to tissue injury and functional deterioration after myocardial ischemia/reperfusion. Especially, mitochondrial reactive oxygen species are capable of opening the mitochondrial permeability transition pore, a harmful event in cardiac ischemia/reperfusion. Thioredoxins are key players in the cardiac defense against oxidative stress. Mutations in the mitochondrial thioredoxin reductase (thioredoxin reductase-2, Txnrd2) gene have been recently identified to cause dilated cardiomyopathy in patients. Here, we investigated whether mitochondrial thioredoxin reductase is protective against myocardial ischemia/reperfusion injury.

Methods and results

In mice, α-MHC-restricted Cre-mediated Txnrd2 deficiency, induced by tamoxifen (Txnrd2-/-ic), aggravated systolic dysfunction and cardiomyocyte cell death after ischemia (90 minutes) and reperfusion (24 hours). Txnrd2-/-ic was accompanied by a loss of mitochondrial integrity and function, which was resolved on pretreatment with the reactive oxygen species scavenger N-acetylcysteine and the mitochondrial permeability transition pore blocker cyclosporin A. Likewise, Txnrd2 deletion in embryonic endothelial precursor cells and embryonic stem cell-derived cardiomyocytes, as well as introduction of Txnrd2-shRNA into adult HL-1 cardiomyocytes, increased cell death on hypoxia and reoxygenation, unless N-acetylcysteine was coadministered.

Conclusions

We report that Txnrd2 exerts a crucial function during postischemic reperfusion via thiol regeneration. The efficacy of cyclosporin A in cardiac Txnrd2 deficiency may indicate a role for Txnrd2 in reducing mitochondrial reactive oxygen species, thereby preventing opening of the mitochondrial permeability transition pore."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.111.059253"xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"David R."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Schulz S."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Schroeder M."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Schneider M."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Lange P."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Schmitt S."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Conrad M."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Sinowatz F."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Zischka H."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Bauersachs J."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Mandal P.K."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Brielmeier M."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Franz W.M."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Ziegler T."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Jeremias I."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Hinkel R."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Kupatt C."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Becker B.F."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Horstkotte J."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Kiermayer C."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Widder J."xsd:string
http://purl.uniprot.org/citations/22144571http://purl.uniprot.org/core/author"Perisic T."xsd:string
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