Mitochondrial thioredoxin reductase is essential for early postischemic myocardial protection.
Abstract | BACKGROUND: 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:
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Authors | Jan Horstkotte, Tamara Perisic, Manuela Schneider, Philipp Lange, Melanie Schroeder, Claudia Kiermayer, Rabea Hinkel, Tilman Ziegler, Pankaj K Mandal, Robert David, Sabine Schulz, Sabine Schmitt, Julian Widder, Fred Sinowatz, Bernhard F Becker, Johann Bauersachs, Michael Naebauer, Wolfgang M Franz, Irmela Jeremias, Markus Brielmeier, Hans Zischka, Marcus Conrad, Christian Kupatt |
Journal | Circulation
(Circulation)
Vol. 124
Issue 25
Pg. 2892-902
(Dec 20 2011)
ISSN: 1524-4539 [Electronic] United States |
PMID | 22144571
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Free Radical Scavengers
- Sulfhydryl Compounds
- Cyclosporine
- Thioredoxin Reductase 1
- Thioredoxin Reductase 2
- Txnrd1 protein, mouse
- Txnrd2 protein, mouse
- Acetylcysteine
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Topics |
- Acetylcysteine
(pharmacology)
- Animals
- Cell Death
(drug effects, physiology)
- Cells, Cultured
- Cyclosporine
(pharmacology)
- Embryonic Stem Cells
(cytology)
- Endothelial Cells
(cytology)
- Enzyme Inhibitors
(pharmacology)
- Free Radical Scavengers
(pharmacology)
- Gene Expression Regulation, Enzymologic
(physiology)
- Hematopoietic Stem Cells
(cytology)
- Mice
- Mice, Knockout
- Mitochondria
(enzymology)
- Myocardial Reperfusion Injury
(drug therapy, metabolism, pathology, physiopathology)
- Myocytes, Cardiac
(cytology)
- Oxidative Stress
(drug effects, physiology)
- Sulfhydryl Compounds
(metabolism)
- Thioredoxin Reductase 1
(genetics, metabolism)
- Thioredoxin Reductase 2
(genetics, metabolism)
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