Cell growth of the mouse SDHC mutant cells was suppressed by apoptosis throughout mitochondrial pathway.
SDHC E69 cells, which overproduce superoxide anions in their mitochondria, were previously established that had a mutation in the SDHC gene of complex II of the respiratory chain. We now demonstrate that tumors formed by NIH 3T3 and SDHC E69 cells showed significant histological differences. Cytoplasmic cytochrome c release from mitochondria was significantly elevated in SDHC E69 cells and was likely caused by superoxide anion overproduction from mitochondria. In addition, the p53 and Ras signal transduction pathways were activated by oxidative stress and may play a key role in the supernumerary apoptosis in SDHC E69 cells. Our results suggest that the development and growth characteristics of hereditary paragangliomas, which are defective in the same complex of electron transport as mouse SDHC E69 cells, may be caused by apoptosis induction by mitochondrial oxidative stress.
Miyazawa
Masaki
M
Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Ishii
Takamasa
T
Kirinashizawa
Mika
M
Yasuda
Kayo
K
Hino
Okio
O
Hartman
Philip S
PS
Ishii
Naoaki
N
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D053181:Caspase 8 / Q000502:physiology; D053453:Caspase 9 / Q000502:physiology; D061945:Caspase Inhibitors; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D061945:Caspase Inhibitors; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D045304:Cytochromes c; D053181:Caspase 8; D053453:Caspase 9; D018631:ras Proteins