title: Damage to mitochondrial respiration chain is related to phospholipase A2 activation caused by tumor necrosis factor.
abstract: Tumor necrosis factor (TNF) has been shown to be cytotoxic to tumor cell lines in vitro, but the mechanism by which TNF exerts its cell growth-regulatory effects is not known. In this report, we used various inhibitors to investigate the sequence of events that lead to cytotoxic effects of TNF on L.P3 cells, a highly sensitive, murine fibroblast cell line. Our results indicate that mitochondrial respiration chains are damaged by a hydroxyl radical at an early stage of the cell lysis after TNF treatment. This event is followed by the activation of phospholipase A2, and finally leads to cell lysis.
authors.affiliation: Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Higuchi
authors.forename: K
authors.initials: K
authors.lastname: Shirotani
authors.forename: N
authors.initials: N
authors.lastname: Higashi
authors.forename: S
authors.initials: S
authors.lastname: Toyoshima
authors.forename: T
authors.initials: T
authors.lastname: Osawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D008555:Melitten / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects*; D010741:Phospholipases A / Q000187:drug effects*; D054467:Phospholipases A2; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005609:Free Radicals; D006878:Hydroxides; D014409:Tumor Necrosis Factor-alpha; D008555:Melitten; D016718:Arachidonic Acid; D017665:Hydroxyl Radical; D010741:Phospholipases A; D054467:Phospholipases A2