Abstract
Mitochondrial thioredoxin (mtTrx) can be oxidized in response to inducers of oxidative stress; yet the functional consequences of the oxidation have not been determined. This study evaluated the redox status of mtTrx and its association to oxidant-induced apoptosis. Results showed that mtTrx was oxidized after exposure to peroxides and diamide. Overexpression of mtTrx protected against diamide-induced oxidation and cytotoxicity. Oxidation of mtTrx was also achieved by knocking down its reductase; and lead to increased susceptibility to cell death. The data indicate that the redox status of mtTrx is a regulatory mechanism underlying the vulnerability of mitochondria to oxidative injury.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Death / drug effects
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Diamide / pharmacology
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Gene Expression / drug effects
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Humans
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Membrane Potentials / drug effects
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Mitochondria / drug effects*
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Mitochondrial Membranes / drug effects
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Oxidants / pharmacology*
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Oxidation-Reduction / drug effects
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Oxidative Stress / drug effects
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Peroxides / pharmacology
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Thioredoxin Reductase 2
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Thioredoxin-Disulfide Reductase / deficiency
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Thioredoxins / metabolism*
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Time Factors
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tert-Butylhydroperoxide / pharmacology
Substances
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Oxidants
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Peroxides
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Diamide
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Thioredoxins
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tert-Butylhydroperoxide
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TXNRD2 protein, human
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Thioredoxin Reductase 2
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Thioredoxin-Disulfide Reductase