Tumour necrosis factor induced an early release of superoxide and a late mitochondrial membrane depolarization in L929 cells - Increase in the production of superoxide is not sufficient to mimic the action of TNF
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AbstractTumour necrosis factor a (TNF) cytotoxicity is mediated, at least in part, by oxidative stress. One of the post-receptor events shortly after the addition of TNF is the generation of the superoxide anion (O-2. (-)). In the present study, we attempted to examine the role of O-2. (-) in the 2 regulation of mitochondrial membrane potential (Delta Psim) and the release of cytochrome c (cyto c) in L929 cells after stimulation with TNF. Challenge of cells with TNF (50 ng/ml) resulted in an early (30 min after the addition of TNF) increase in the production of O-2. (-). The use of mitochondrial electron transport chain inhibitors such as antimycin A and rotenone could, respectively, potentiate or suppress the TNF-mediated release of O-2. (-) and cytotoxicity. TNF also induced a late (>3 h after the addition of TNF) depolarization in the Delta Psim. Reduction in the release of O-2. (-) by rotenone (50 muM) or thenoyltrifluoroacetone (250 muM) suppressed both the TNF-mediated Delta Psim depolarization and cyto c release. However, increase in the production of O-2. (-) by antimycin A 2 (25 muM) only slightly enhanced the TNF effect in altering the Delta Psim and the release of cyto c. Treating cells with antimycin A alone could not induce a reduction in Delta Psim nor a release of cyto c. Taken together, our results indicate that TNF induced damage in mitochondria in L929 cells. Our data also show that an increase in the production of O-2. (-) was important in the TNF cytotoxicity, but was not sufficient to mimic the action of TNF. Copyright (C) 2001 S. Karger AG, Basel.
All Author(s) ListKo S, Kwok TT, Fung KP, Choy YM, Lee CY, Kong SK
Volume Number10
Issue Number5
Pages326 - 335
LanguagesEnglish-United Kingdom
Keywordsapoptosis; mitochondria; mitochondrial membrane potential depolarization; superoxide; tumour necrosis factor
Web of Science Subject CategoriesBiochemistry & Molecular Biology; Biophysics; Cell Biology

Last updated on 2021-22-09 at 23:53