| Project/Area Number |
07456139
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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 |
Applied veterinary science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
DOI Kunio The University of Tokyo, Graduate School of Agricultural and Life Sciences, Prof., 大学院・農学生命科学研究科, 教授 (70155612)
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| Co-Investigator(Kenkyū-buntansha) |
ITAGAKI Shin-ichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Asso, 大学院・農学生命科学研究科, 助教授 (00159823)
NAKAYAMA Hiroyuki The University of Tokyo, Graduate School of Agricultural and Life Sciences, Asso, 大学院・農学生命科学研究科, 助教授 (40155891)
OZAKI Hiroshi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Asso, 大学院・農学生命科学研究科, 助教授 (30134505)
SHIOTA Kunio The University of Tokyo, Graduate School of Agricultural and Life Sciences, Asso, 大学院・農学生命科学研究科, 助教授 (80196352)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | APOPTOSIS / GALACTOSAMITE / HEPATOCYTE / Ca^<2+> / T-2 toxin / 5-AZACYTIDINE / APOPTOSIS / アポートシス / マウス |
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| Research Abstract |
Details of galactosamine (GalN)-induced apoptosis in mouse hepatocytes were investigated. In the primary hepatocyte cultures treated with GalN,DNA-fragmentation was detected prior to LDH-release from cells to culture medium, and apoptosis was followed by necrosis in the high dose group (20mM). Hepatocyte apoptosis was also induced in mice at 24 hr after GalN-treatment (3mg/kg), and apoptosis was also followed by necrosis in this case.
Immediately after GalN-treatment, an intracellular Ca^<2+>-concentration arose sharply in the primary hepatocyte cultures. In addition, CPZ (Ca^<2+>-calmodulin antagonist) and VR (Ca^<2+>-channel blocker) effectively suppressed hepatocyte apoptosis both in in vitro and in vivo systems when they were administered before GalN-treatment, and this suggests that a rapid increase in intracellular Ca^<2+>-concentration may play an important role in the development of GalN-induced hepatocyte apoptosis. Now we are trying to elucidate why GalN-treatment induces a rapid Ca^<2+>-influx into hepatocytes. On the other hand, hepatocyte necrosis was not suppressed by CPZ- and VR-treatment. Moreover, Fas and p53 had no relation to the induction of apoptosis by GalN.
The mechanism of GalN-induced hapatocyte apoptosis seems to be different from those of T-2 toxin-induced lymphocytic apoptosis and of 5-azacytidine-induced neuronnal apoptosis which were also examined in the present project from the comparative viewpoints.
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