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
Volume41
Issue9
Pagination1041-6
Date Published2007 Sep
ISSN1071-5762
KeywordsAnimals, Antioxidants, Butylated Hydroxyanisole, Cell Line, Tumor, Humans, Mice, Mitochondria, Necrosis, Tumor Necrosis Factor-alpha
Abstract

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.

DOI10.1080/10715760701557153
Alternate JournalFree Radic. Res.
Citation Key10.1080/10715760701557153
PubMed ID17729122
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom