Ultrastructural basis for the transition of cell death mode from apoptosis to necrosis in menadione-treated osteosarcoma 143B cells.
Time-dependent ultrastructural changes of menadione-treated human osteosarcoma 143B cells were correlated with those in their stainability to Annexin V and propidium iodide (PI). Populations of both apoptotic (Annexin V(+)/PI(-)) and necrotic (Annexin V(+)/PI(+)) cells, judged by flow cytometry, began to increase at 2 h after menadione treatment. The former reached a maximum at 6 h followed by abrupt decreases thereafter, while the latter continued to increase. Electron microscopically, cells obtained at 6 h after the menadione treatment consisted of mixed populations of cells with typical apoptotic features and those with a mixture of apoptotic and necrotic features, while cells obtained at 8-24 h consisted exclusively of cells with a mixture of apoptotic and necrotic features. Thus, necrotic cells, as judged by flow cytometry, were in a transitional state of cell death mode from apoptosis to necrosis and are thus designated as 'intermediate cells'. Lack of apoptotic bodies, judged by flow cytometric analysis on sub-G1 nuclei and by electron microscopy in menadione-treated cells, suggested that the transition of cell death mode from apoptosis to necrosis occurred before the apoptotic processes were completed. Effects of N-acetylcysteine and Z-VAD-fmk on menadione-induced ultrastructural changes were also studied.
Kamiński
Marcin
M
Department of Cell Biology and Molecular Pathology, Medical University of Gdańsk. ul. Debinki 1, 80-210, Gdańsk, Poland.
Masaoka
Makoto
M
Karbowski
Mariusz
M
Kedzior
Jakub
J
Nishizawa
Yuji
Y
Usukura
Jiro
J
Wakabayashi
Takashi
T
D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000473:pathology; D002467:Cell Nucleus / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology; D009336:Necrosis; D012516:Osteosarcoma / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D024483:Vitamin K 3 / Q000494:pharmacology*
D000933:Antifibrinolytic Agents; D024483:Vitamin K 3