| Project/Area Number |
14370751
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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 |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
TATSUYA Takano Teikyo Univ., Pharm.Sci., Prof., 薬学部, 教授 (40124995)
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| Co-Investigator(Kenkyū-buntansha) |
HOMMA Kouichi Teikyo Univ., Pharm.Sci., Ass.Prof., 助教授 (90251438)
MORI Masahiro Teikyo Univ., Pharm.Sci, Ass.Res., 助手 (00230079)
FUJIMOTO Yasuyuki Teikyo Univ., Pharm.Sci, Ass.Res., 助手 (60317724)
板部 洋之 帝京大学, 薬学部, 助教授 (30203079)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Apoptosis / Necrosis / Foam cell / Hyperlipidemia / Atherogenesis / Macrophage / 256C抗体 / リン脂質 / 動脈硬化 / コレステロール / 脂質球 |
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| Research Abstract |
To explore the fate of the macrophage-derived foam cells expressed phosphatidylcholine (PC)-free cholestrol (FC) complex, we have established the culture system of the foam cells up to 14 days. 1774.1 murine macrophage cells were incubated with small amount of hyperlipidemic sera obtained from WHHL rabbits for 24 h to induce foam cells, and then the foam cells were cultured in fresh media without WHHL sera. Using WHHL hyperlipidemic sera, the foam cells increased cellular FC contents and in concomitant PC-FC complex appeared in lipid droplets which was recognized by an atheroma-specific monoclonal antibody ASH1a/256C. The foam cells express PC-FC complex detected by the ASH1a/256C antibody at day 4, then 60 % of the died by day 7. Interestingly, the nuclei of the many cells became smaller and fainter as early as day 4, suggesting degradation of nuclei. At day 7 or later, there appeared lipid droplets- containing cells devoid of nucleus. Staining the cells with TUNEL method as well as annexin V shows these cells could be died by apoptotic pathway. The foam cells at day 4 expressed the novel unfolded protein response (UPR) markers CHOP and XBP-1 only when the foam cell induced by WHHL serum. Human hyperlipidemic sera also induced PC-FC complex formation and following foam cell death by apoptotic pathway. These observations suggest that increase in PC-FC complex closely related with the foam cell apoptosis through FC induced UPR pathway.
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