Tunicamycin potently inhibits tumor necrosis factor-induced hepatocyte apoptosis.
The protein glycosylation inhibitor tunicamycin protected male BALB/c mice from tumor necrosis factor alpha-induced liver failure. Tunicamycin also inhibited tumor necrosis factor-induced cell death in primary hepatocyte cultures with a median inhibitory concentration of 8 nM, but not in the tumor cell line WEHI 164 clone 13. Hepatocyte death in our culture system was characterized by DNA fragmentation and apoptotic changes. These two characteristic signs of programmed cell death were also inhibited by tunicamycin treatment. These data suggest that protein glycosylation is an early and causal event of tumor necrosis factor (TNF)-induced parenchymal cell death in the liver.
Leist
M
M
Faculty of Biology, University of Konstanz, Germany.
Wendel
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity; D014415:Tunicamycin / Q000494:pharmacology*
D002843:Chromatin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014415:Tunicamycin; D003609:Dactinomycin; D004247:DNA