Role of mitochondria in the switch mechanism of the cell death mode from apoptosis to necrosis—Studies on ρ0 cells

Detailed mechanisms of the switch of the cell death mode from apoptosis to necrosis remain to be solved, although the intracellular level of ATP and that of free radicals have been postulated to be the major factors involved in the mechanisms. In the present study menadione (MEN)-induced cell injury...

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Bibliographic Details
Published in:Journal of electron microscopy 2005-04, Vol.54 (2), p.127-138
Main Authors: Wochna, Agnieszka, Niemczyk, Edyta, Kurono, Chieko, Masaoka, Makoto, Majczak, Anna, Kędzior, Jakub, Słomińska, Ewa, Lipiński, Marcin, Wakabayashi, Takashi
Format: Article
Language:English
Subjects:
apoptosis
intracellular ATP
menadione
necrosis
superoxide
ρ0 cells
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Summary:Detailed mechanisms of the switch of the cell death mode from apoptosis to necrosis remain to be solved, although the intracellular level of ATP and that of free radicals have been postulated to be the major factors involved in the mechanisms. In the present study menadione (MEN)-induced cell injury processes were studied using ρ0 cells derived from human osteosarcoma 143B cells and parental ρ+ cells co-treated with inhibitors of electron transfer chain of mitochondria or oligomycin, an inhibitor of ATP synthesis. Treatment of ρ+ cells with 100 μM MEN induced apoptosis, which reached the maximum at 6 h, and was followed by an abrupt decrease thereafter, while necrotic cells (NC) increased continuously when they were judged by Annexin V and PI double staining. On the other hand, MEN induced apoptotic and necrotic changes much faster in ρ0 cells compared to ρ+ cells. The frequency to find apoptotic cells (AP) in the former cells was distinctly smaller than that to find NC judged by Annexin V and PI double staining. Electron microscopically, a major population of ρ0 cells treated with MEN for 6 h consisted of intermediate cells, and a small number of AP co-existed. At 9 h of the treatment intermediate cells were exclusively seen, and AP were hardly detected. When parental ρ+ cells were treated with MEN in the presence of oligomycin or oligomycin plus antimycin A both apoptotic and necrotic changes of the cells were distinctly accelerated. The intracellular level of superoxide in ρ0 cells continuously increased after the MEN treatment, whereas that of ATP remained distinctly low before and after the MEN treatment compared to that in ρ+ cells. These data suggest that the intracellular level of superoxide may be a key factor controlling the switch from apoptosis to necrosis.
ISSN:0022-0744
2050-5698
1477-9986
2050-5701
DOI:10.1093/jmicro/dfi031