mtDNA‐depleted U937 cells are sensitive to TNF and Fas‐mediated cytototxicity
- 27 November 1995
- journal article
- Published by Wiley in FEBS Letters
- Vol. 376 (1-2), 15-18
- https://doi.org/10.1016/0014-5793(95)01236-1
Abstract
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-ϱ°) were resistant to TNF, but this was due to the loss of its 55 kDa receptor. U937-ϱ° 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 generationKeywords
This publication has 26 references indexed in Scilit:
- CrmA, a Poxvirus-encoded Serpin, Inhibits Cytotoxic T-lymphocyte-mediated ApoptosisPublished by Elsevier BV ,1995
- Oxygen Stress Induces an Apoptotic Cell Death Associated with Fragmentation of Mitochondrial GenomeBiochemical and Biophysical Research Communications, 1995
- Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)Nature, 1995
- No requirement of reactive oxygen intermediates in Fas‐mediated apoptosisFEBS Letters, 1994
- Unraveling Function in the TNF Ligand and Receptor FamiliesScience, 1994
- Molecular mechanisms of tumor necrosis factor‐induced cytotoxicityFEBS Letters, 1994
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993
- P80 form of the human tumor necrosis factor receptor is involved in DNA fragmentationFEBS Letters, 1993
- A novel domain within the 55 kd TNF receptor signals cell deathCell, 1993
- Recurrent Seyfert activity in spiral galaxy nucleiNature, 1981