mtDNA-depleted U937 cells are sensitive to TNF and Fas-mediated cytotoxicity.
It has been proposed that TNF cytotoxicity is mediated by reactive oxygen intermediates generated by uncoupling of mitochondrial respiration. We have compared sensitive U937 cells and derived cell lines depleted of mtDNA for their ability to undergo TNF- and Fas-induced apoptosis. Cells lacking around 98% of mtDNA were still sensitive to TNF-induced apoptosis. U937 cells devoid of mtDNA (U937-rho degree) were resistant to TNF, but this was due to the loss of its 55 kDa receptor. U937-rho degree cells were also resistant to docosahexaenoic acid, which causes U937 cell death by lipid peroxidation. These cells were sensitive to anti-Fas toxicity. The results indicate that TNF and Fas-induced toxicity occurs by a mechanism mostly independent of mitochondrial free radical generation.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Zaragoza, Spain.
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S
Gamen
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Anel
J
J
Montoya
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Marzo
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Piñeiro
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J
Naval
D000654:Amobarbital / Q000494:pharmacology; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D006801:Humans; D015463:Leukemia, Prolymphocytic / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000276:immunology*
D000906:Antibodies; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D012402:Rotenone; D004281:Docosahexaenoic Acids; D013804:Thenoyltrifluoroacetone; D000654:Amobarbital