Grant-in-Aid for Overseas Scientific Survey.
|Research Institution||Kagawa Medical School|
ICHIKAWA Yoshiyuki Kagawa Medical School, Professor, 医学部, 教授 (60028355)
大西 平 香川医科大学, 医学部(アルバータ大学・医学部), 講師(研究員) (50211107)
山村 卓 国立循環器病センター研究所, 病因部, 室長 (20132938)
山本 章 国立循環器病センター研究所, 副所長 (00028408)
原 斉 アルバータ大学, 医学部, 研究員
横山 信治 アルバータ大学, 医学部, 教授 (10142192)
YAMAMOTO Akira Research Institute of National Cardiovascular Center, Vice Director
YAMAMURA Taku Research Institute of National Cardiovascular Center, Head
YOKOYAMA Shinji University of Alberta, Professor
OHNISHI Taira Kagawa Medical School, Associate Professor (University of Alberta, research Asso
|Project Fiscal Year
1990 – 1992
Completed(Fiscal Year 1992)
|Budget Amount *help
¥9,500,000 (Direct Cost : ¥9,500,000)
Fiscal Year 1992 : ¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 1991 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1990 : ¥3,000,000 (Direct Cost : ¥3,000,000)
|Keywords||Cholesterol Reverse Transport System / Apolipoprotein / Discoidal Highdensity Plasma Lipoprotein / Lipid Microemulsion / Pyrene Compound / コレステロール逆転送系 / アポリポタンパク質 / ディスコイダルHDL / 脂質転送蛋白質 / ピレン-標識脂質 / 脂質人工粒子 / ピレンーコレステロ-ル / コレステロ-ル逆転送系 / 脂質転送蛋白質活性化因子 / ピレン / アポリポタンパクA / ディスコイダル HDL / マウス腹腔マクロファ-ジ|
The first step of cholesterol reverse transport from peripheral cells to liver is the efflux of cholesterol from the surface of cells by plasma lipoprotein. To clarify the mechanism of the step, we used rat peritoneal macrophage and lipid microemulsion with apolipoprotein A-I. Free cholesterol was released from macrophage when macrophage was incubated with microemulsion and apolipoprotein. Furthermore, cholesterol and phospholipid were released into the incubation medium when it was incubated with only free apolipoprotein. We found that the addition of free apolipoprotein to macrophage caused the formation of discoidal HDL-like particle. The same result was observed using fibroblast and smooth muscle cell but the extent of the efflux of cholesterol from smooth muscle cell was less than that from other cells, The HDL-like particle was quickly disappeared when incubated with lipid microemulsion. Therefore, we concluded that cholesterol efflux from cells to plasma lipoprotein occurred via
discoidal HDL-like particle.
Free cholesterol released from cells is esterified on the surface of HDL and redistributed into plasma lipoproteins. The transfer reaction of lipid between plasma lipoproteins is catalyzed by plasma lipid transfer protein(LTP). We have established the purification of LTP from human plasma. To estimate the accurate transfer rate by LTP, we applied the new method using lipid microemulsion containing fluorescence-labeled lipid (pyrene compound) to the measurement of the transfer rate. The coverage of lipid microemulsion with apolipoprotein was necessary for the lipid transfer by LTP. There was little difference between the transfer rate of cholesteryl ester and triglyceride, however, cholesteryl ester was selectively transferred between microemulsion by LTP when microemulsion contained both cholesteryl ester and triglyceride. The difference of the selectivity of cholesteryl ester over triglyceride was more than a hundred times. Therefore the net movement of cholesteryl ester seemed to occur only between HDL-LDL cholesteryl ester pool and VLDL because there was no net movement of cholesteryl ester between cholesteryl ester-rich particles.