title: A possible role of oxidative stress in the switch mechanism of the cell death mode from apoptosis to necrosis--studies on rho0 cells.
abstract: Apoptosis is induced not only during morphogenesis and embryogenesis but also under various pathological conditions, especially related to oxidative stress. Apoptotic cells are phagocytized by neighboring cells while necrotic cells cause local and general reactions sometimes lethal to our bodies. Data have been accumulated to demonstrate that the switch of the cell death mode from apoptosis to necrosis does occur. However, detailed mechanisms involved in the switch mechanism remain unsolved although decreases in the intracellular level of ATP and a burst in the cellular level of reactive oxygen species (ROS) have been proposed. Recently, we have shown that the population of apoptotic cells reaches maximum in human osteosarcoma 143B cells treated for 6h with menadione (MEN) while necrotic cells become predominant at 9h of the treatment. In the present study we have attempted to clarify the role of cellular ATP in the switch mechanism using rho(0) cells derived from human osteosarcoma rho+ cells. Results are summarized as follows: (1) Apoptotic and necrotic changes in rho(0) cells are much faster than rho+ cells after the treatment with MEN. (2) Cellular level of ATP in rho(0) cells remains essentially in the same level before and after the MEN-treatment while intracellular levels of superoxide continuously increase after the MEN-treatment. (3) rho+ cells treated with MEN in the presence of antimycin A plus oligomycin show similar changes to those of MEN-treated rho(0) cells. (4) MEN-induced increases in the cellular level of superoxide are distinctly suppressed by inhibitors of NADPH oxidase. These results suggest that the intracellular level of superoxide may be a key factor directly related to the switch mechanism from apoptosis to necrosis, and that decreases in cellular level of ATP accelerate both apoptotic and necrotic changes of the cells.
authors.affiliation: Department of Cell Biology and Molecular Pathology, Medical University of Gdańsk, 80-210 Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wochna
authors.forename: Edyta
authors.initials: E
authors.lastname: Niemczyk
authors.forename: Chieko
authors.initials: C
authors.lastname: Kurono
authors.forename: Makoto
authors.initials: M
authors.lastname: Masaoka
authors.forename: Jakub
authors.initials: J
authors.lastname: Kedzior
authors.forename: Ewa
authors.initials: E
authors.lastname: Słomińska
authors.forename: Marcin
authors.initials: M
authors.lastname: Lipiński
authors.forename: Takashi
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000968:Antimycin A / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008854:Microscopy, Electron; D009336:Necrosis / Q000503:physiopathology*; D009840:Oligomycins / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D014407:Tumor Cells, Cultured; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D009840:Oligomycins; D000968:Antimycin A; D024483:Vitamin K 3