| Project/Area Number |
15591401
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kyoto University |
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Principal Investigator |
HATANO Etsuro Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80359801)
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| Co-Investigator(Kenkyū-buntansha) |
IKAI Iwao Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (60263084)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | hepatic ischemia reperfusion / bile duct ligation / endoplasmic reticulum stress / apoptosis / caspase-12 / 肝虚血再灌流 / caspase-12 |
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| Research Abstract |
Blocking of death receptor-induced and mitochondrial apoptotic pathways is insufficient to inhibition of hepatic ischemia/reperfusion injury and cholestatic injury. Therefore, we focus on endoplasmic reticulum(ER) stress-induced apoptotic pathway, so-called third apoptotic pathway, in these liver injuries. Our aim of this study is to clarify the role of ER stress-induced apoptotic signaling pathway in mouse hepatic ischemia/reperfusion and cholestatic injury. Ischemia/reperfusion injury was induced by ischemia in 70% of the liver for 90 minutes followed by reperfusion in C57BL6 mice. Cholestatic liver injury was induced by ligation of the bile duct in C57BL6 mice. RT-PCR demonstrated the elevation of mRNA levels in GADD 153 immediately after reperfusion and in GRP78 12 hours after reperfusion. Western blotting showed the enhanced expression of GADD153 3 hours after reperfusion. The mRNA levels in GRP78 and caspase-12 were elevated 12 hours after reperfusion. The expression of GRP78 and GADD153 were elevated in both mRNA and protein levels 24 hours after bile duct-ligation. In both models, the decrease in procaspase-12 and the increase in the number of apoptotic cell death were shown by the Western blotting and TUNEL assay, respectively. In conclusion, this study is a first report showing that GADD153 induced by ER stress is involved in apoptosis in hepatic injury after reperfusion and obstructive jaundice. However, the specific role of GADD153 in these hepatic injuries is not clear. Now we are conducting the additional experiment using GADD153 knock out mice.
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