| Project/Area Number |
14570500
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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 |
Gastroenterology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
TAKIKAWA Yasuhiro Iwate Medical University, First department of internal Medicine, Assistant Professor, 医学部, 講師 (50254751)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Ryujin Iwate Medical University, First department of internal Medicine, Instructor, 医学部, 助手 (70316355)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Hepatocyte apoptosis / Phosphatidyl serine / Blood coagulation / Massive hepatocyte death / Pros tagland in / Bcl-xL / 劇症肝炎 / 肝細胞 / アポトーシス |
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| Research Abstract |
1. Acceleration of blood coagulation by apoptotic hepatocellular carcinoma HepG2 cells
1) The apoptosis of Hep G2 cells was induced by staurosporin (STS).
2) Phosphatidyl serine (PS) expression was detected by confocal microscopy with FITC-annexin V, a specific inhibitor of PS activity.
3) The STS treatment of HepG2 cells significantly accelerated thrombin generation, which was determined using a thrombin-specific chromogenic substrate after exposing the cells to activated factor X, CaCl_2 and prothrombin. 4) The increase in thrombin generation by STS treatment was abolished following pretreatment with annexin V.
These data indicate that apoptotic hepatocytes accelerate blood coagulation through the expression of a PS-dependent procoagulant surface.
2. Prostaglandin receptor EP4 agonist (GPEP4A) suppression of Fas-induced apoptosis in HepG2 cells through direct Bcl-xL induction.
1) GPEP4A suppressed Fas-induced apoptosis of HepG2 cells, whereas indomethacin accelerated it.
2) PGE2RA significantly increased the expression levels of the Bcl-xL protein and mRNA; indomethacin decreased the expression levels, of Mdl proteins.
These data indicate that direct Bcl-xL induction plays an important role in the hepatocyte protective effect induced by PGE2R-A.
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