| Project/Area Number |
08671196
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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 |
内分泌・代謝学
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| Research Institution | Fukuoka University |
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Principal Investigator |
MATSUNAGA Akira Fukuoka University, School of Medicine, Lecture, 医学部, 講師 (60221587)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Jun Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (90122697)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | apolipoprotein A-I / apo A-I / mutation / fractional catabolic rate / recombinant / expression / cholestrol efflux / アポリポ蛋白 / 遺伝子 / 変異体 |
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| Research Abstract |
It is widely assumed that high density lipoproteins (HDL) exert their antiatherogenic role by contributing to the reverse transport of excess cholesterol from peripheral cells to the liver and steoidogenic organs. In complexes with HDL,apolipoprotein (apo) A-I acts as the most potent activator of the plasma enzume lecithin : chlesterol acyltransferase (LCAT) and increases cholesterol efflux from peripheral tissues. In our laboratory, ten different apo A-I mutations were characterized. In this project, functional consequences of the mutation were examined by expressing the mutated and wild-type recombinant proapo (r-proapo) A-I cDNAs in E.coli. We produced four different mutations of r-proapo A-I,proapo A-I (Tyr100His) Karatsu, proapo A-I (Trp108Arg) Tsushima, proapo A-I (Vall56Glu) Oita, proapo A-I (Glu235*0) Nichinan Cholesterol efflux to r-proapo A-I (Glu235*0) Nichinan from mouse peritoneal macrophages converted with [^3H] cholesterol-labeled acetylated LDL was decreased by 54% when compared that of normal r-proapo A-I.In vivo turnover studies in normal rabbits demonstrated that the r-proapo A-I Nichinan was rapidly cleared by 22% compared with normal r-proapo A-I.We conclude that the apo A-I (Glu235*0) Nichinan induced a critical structural change of the carboxyl-terminal domain of apo A-I for cellular cholesterol efflux and increased catabolism of the apo A-I,resulting in low HDL cholesterol level. We are going to continue the next experiment for functional analysis of mutant apo A-I.
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