Project/Area Number |
02670105
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
General medical chemistry
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
MURAKAMI Motonobu Dept of Geriatric Med, Faculty of Med, Kyoto University, Associate Professor., 医学部, 助教授 (10157761)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Mituhiro Dept of Geriatric Med, Faculty of Med, Kyoto University, Instructor, 医学部, 助手 (20229579)
NAGANO Yutaka Dept of Geriatric Med, Faculty of Med, Kyoto University, Instructor., 医学部, 助手 (80228048)
|
Project Period (FY) |
1990 – 1992
|
Project Status |
Completed (Fiscal Year 1992)
|
Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | beta-VLDL / macrophage / fibroblast / WHHL rabbit / LDL receptor / B-VLDL / 動脈硬化 / βVLDL / 受容体 / マクロファ-ジ / WHHLウサギ |
Research Abstract |
The receptor-mediated uptake of rabbit hypercholesterolemic very low density lipoprotein (beta-VLDL) was studied in fibroblasts and peritoneal macrophages from normal and Watanabe heritable hyperlipidemic (WHHL) rabbits. Fibroblasts and macrophages of WHHL rabbits degraded [^<123>I]beta-VLDL with saturable, high affinity mechanism, and the amount of [^<123>I]beta-VLDL degraded by WHHL rabbit cells were about 30% of that degraded by control cells. In these cells, the degradation of [^<123>I]beta-VLDL was completely inhibited by polyclonal antibodies to low density lipoprotein (LDL) receptor. An immunoprecipitation study showed that WHHL macrophages synthesized mature mutant LDL receptors. In a ligand blotting study, normal and WHHL rabbit fibroblasts recognized beta-VLDL as a single band, size of which is 160kd. These results indicate that uptake of beta-VLDL to WHHL rabbit fibroblasts and macrophages is mediated by mutant LDL receptor. Our data suggest that VLDL of WHHL rabbit, which is very similar with beta-VLDL, is involved in foam cell formaiton of macrophages and development of atheromatous plaque.
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