Mitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells.

TitleMitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells.
Publication TypeJournal Article
Year of Publication2007
AuthorsJarvis, RM, Göttert, J, Murphy, MP, Ledgerwood, EC
JournalFree Radic Res
Date Published2007 Sep
KeywordsAnimals, Antioxidants, Butylated Hydroxyanisole, Cell Line, Tumor, Humans, Mice, Mitochondria, Necrosis, Tumor Necrosis Factor-alpha

Mitochondrial production of reactive oxygen species (ROS) is widely reported as a central effector during TNF-induced necrosis. The effect of a family of mitochondria-targeted antioxidants on TNF-induced necrosis of L929 cells was studied. While the commonly used lipid-soluble antioxidant BHA effectively protected cells from TNF-induced necrosis, the mitochondria-targeted antioxidants MitoQ(3), MitoQ(5), MitoQ(10) and MitoPBN had no effect on TNF-induced necrosis. Since BHA also acts as an uncoupler of mitochondrial membrane potential, two additional uncouplers were tested. FCCP and CCCP both provided dose-dependent inhibition of TNF-induced necrosis. In conclusion, the generation of mitochondrial ROS may not be necessary for TNF-induced necrosis. Instead, these results suggest alternative mitochondrial functions, such as a respiration-dependent process, are critical for necrotic death.

Alternate JournalFree Radic. Res.
Citation Key10.1080/10715760701557153
PubMed ID17729122
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom