Mitochondrial formation of hydrogen peroxide is causally linked to the antimycin A-mediated prevention of tert-butylhydroperoxide-induced U937 cell death.
Antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), both of which bind to the same site of complex III, prevented U937 cell killing promoted by tert-butylhydroperoxide (tB-OOH). This cytoprotection was not directly caused by inhibition of electron transport or reduced formation of tB-OOH-derived toxic species, but rather appeared to be the consequence of a mechanism involving mitochondrial formation of hydrogen peroxide. Ubisemiquinone was most likely the electron donor allowing the formation of superoxides and, as a consequence, of hydrogen peroxide.
Istituto di Farmacologia e Farmacognosia and Centro di Farmacologia Oncologica Sperimentale, Università di Urbino, Italy.
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D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006912:Hydroxyquinolines / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010545:Peroxides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide
D000900:Anti-Bacterial Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D006912:Hydroxyquinolines; D010545:Peroxides; C001333:2-(n-heptyl)-4-hydroxyquinoline N-oxide; D000968:Antimycin A; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D014450:Electron Transport Complex III