Mitochondrial thioredoxin in regulation of oxidant-induced cell death.
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.
Chen
Yan
Y
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cai
Jiyang
J
Jones
Dean P
DP
D016923:Cell Death / Q000187:drug effects; D003958:Diamide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D051336:Mitochondrial Membranes / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase / Q000172:deficiency; D013879:Thioredoxins / Q000378:metabolism*; D013997:Time Factors; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D016877:Oxidants; D010545:Peroxides; D003958:Diamide; D013879:Thioredoxins; D020122:tert-Butylhydroperoxide; C516127:TXNRD2 protein, human; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase