Expression of the Apoptosis-Mediator Fas Is Enhanced by Dysfunctional Mitochondria
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概要
- 論文の詳細を見る
We applied an antibody against an apoptosis mediator, Fas/APO-1/CD95,to HeLa-derived cells that completely lack mitochondrial DNA (mtDNA) or have mutant mtDNAs. The anti-Fas antibody killed the cells completely lacking mtDNA (EB8), at concentrations as low as 1ng/ml, but not control cells harboring wild-type mtDNA (Ft2-11). TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling) and analysis of fragmented DNA indicated that the cell death of EB8 was due to apoptosis. The antibody was cytotoxic to other two cell lines harboring mutant mtDNA with a point mutation or a large-scale deletion. RT-PCR (reverse transcriptase-polymerase chain reaction) showed that the mRNA content of the Fas gene was 2 to 19-fold higher in the cells with deficient mtDNA than in the control cells. In addition, the expressed Fas protein was detected by immunohistochemical staining in the cells without mtDNA but not in the control cells. Incubating the cells containing wild-type mtDNA with the respiratory inhibitors rotenone and antimycin A enhanced the content of mRNA of the Fas gene 2 to 4-fold and sensitized cells to the antibody. Thus, defects in mitochondria caused apoptotic cell death by anti-Fas antibody and enhanced Fas gene expression.
- 日本医科大学の論文
- 1997-03-25
著者
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Ohta S
Department Of Biochemistry And Cell Biology Institute Of Development And Aging Sciences Graduate Sch
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Ohta Shigeo
日本医科大学老人病研究所 分子細胞構造学
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Aoki Satoshi
日本医科大学千葉北総病院 循環器内科
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MORI Takashi
the Departments of Thoracic Surgery
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Hayashi Junichi
The Institute Of Biological Sciences University Of Tsukuba
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Asoh Sadamitsu
The Division of Biochemistry
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Ohta Shigeo
The Division of Biochemistry
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Asoh Sadamitsu
Department Of Biochemistry And Cell Biology Institute Of Development And Aging Sciences Graduate Of
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Hayashi Jun-ichi
Graduate School Of Life And Environmental Sciences University Of Tsukuba
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Mori Takashi
The Department Of Surgery National Kinki Central Hospital
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Mori Takashi
Department Of Biochemistry And Cell Biology Institute Of Development And Aging Sciences Graduate Sch
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