| Project/Area Number |
03671134
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | TEIKYO UNIVERSITY (1992)
The University of Tokyo (1991) |
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Principal Investigator |
TERAMOTO Tamio TEIKYO UNIV. SCHOOL OF MEDICINE ASSOCIATE PROF., 医学部, 助教授 (20133077)
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| Co-Investigator(Kenkyū-buntansha) |
KINOSHITA Makoto TEIKYO UNIV. SCHOOL OF MEDICINE LECTURE, 医学部, 講師 (70186295)
MATSUSHIMA Teruhiko UNIV.OF TSUKUBA INSTITUTE OF CLIN.MED. LECTURER, 臨床医学系, 講師 (60199792)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | CHOLESTEROL ESTER TRANSFER PROTEIN / APOLIPOPROTEIN E / REVERES CHOLESTEROL TRANSPORT / APOLIPOPROTEIN E DEFICIENCY / CETP DEFICIENCY / コレステロ-ルエステル転送蛋白(CETP) / コレステロ-ル逆転送系 / アポ蛋白E損症 |
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| Research Abstract |
In order to explore the regulatory role of apolipoprotein E in cholesterol reverse transport, we studied the effect of apo E on platelet function(1) and on cholesterol ester transfer activity(2).
(1) A patient with apo E deficiency showed evidence of decreased platelet aggregativity in platelet-rich plasma, but normal aggregativity in washed platelets. Both patient's plasma and HDL fraction inhibited platelet aggregation of normal subjects. Patient's HDL reconstituted with recombinant apo E showed further inhibitory effects on platelet function. These results suggest that apo E is a potent, but not unique, inhibitory factor of HDL. (2) The direct effect of apolipoprotein (apo) E on cholesteryl ester transfer protein (CETP) activity was studied, using lipoproteins from an apo E deficiency as a model system. The transfer of cholesteryl ester (CE) from discoidal bilayer particle (DBP) to very low density lipoprotein (VLDL) was enhanced by incorporation of apo E into VLDL. This enhancement was induced only in the presence of CETP activity. Moreover, after incubation of CETP with VLDL, CETP activity and immunoreactivity were co-eluted with apo E incorporated VLDL (E-VLDL) on a gel filtration column, but little with apo E-free VLDL (C-VLDL), suggesting that E-VLDL had higher affinity for CETP compared to C-VLDL. The supplementation with apo E of the apo E deficient serum enhanced the CETP-mediated changes of amount of CE and triglyceride (TG) in HDL fraction, which were completely inhibited by the addition of the monoclonal antibody against CETP that blocks CETP activity. Our results suggest that 1) apo E enhances the CE and TG transfer between VLDL and HDL via CETP and 2) this effect of apo E may be mediated by enhancing the affinity of CETP for VLDL.
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