| Project/Area Number |
09470270
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KANSAI MEDICAL UNIVERSITY |
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Principal Investigator |
KITAZAWA Yasuhide KANSAI MEDICAL UNIVERSITY, DEPARTMENT OF MEDICINE, LECTURER, 医学部, 講師 (10140261)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEYAMA Naoshi KANSAI MEDICAL UNIVERSITY, DEPARTMENT OF MEDICINE, LECTURER, 医学部, 講師 (00155053)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Cytochrome c / mitochondria / apoptosis / bcl-2 / チトクローム C / microinjector / L929 / TNF-α / zVAD-fmk |
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| Research Abstract |
Reduction of mitochondrial membrane potential (Ψm) and release of cytochrome c from mitochondria appear to be a key events during apoptosis. Apoptosis was induced in IC.DP premast cells by the withdrawal of IL-3. Ψm decreased by 12 h and cytochrome c was detected in the cytosol at 18 h. Despite these changes in the mitochondria after 18 h of IL-3 deprivation, clonogenicity was unaffected when IL-3 was replenished at 18 h. Activation of v-Abl tyrosine kinase in IC.DP cells before IL-3 depletion led to increased levels of Bcl-XL, prevented reduction of Ψm and the release of mitochondrial cytochrome c, and suppressed apoptosis. Activation of v-Abl TK 18 h after withdrawal of IL-3 when < 10% of the cells had died restored Ψm in the remaining cells. These data suggest that v-Abl TK or IL-3 can act downstream of the reduction in Ψm and cytochrome c release from mitochondria to promote long-term cell survival.
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