1992 Fiscal Year Final Research Report Summary
Cell and molecular biological approaches to atherosclerosis in an animal model for familial hypercholesterolemia.
| Project/Area Number |
03404066
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
KITA Toru Dept. of Geriatric Medicine, Faculty of Medicine, Kyoto University, Professor, 医学部, 教授 (60161460)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Motonobu Dept. of Geriatric Medicine, Faculty of Medicine, Kyoto University, Associate Pr, 医学部, 助教授 (10157761)
YOHSIOKA Hideyuki Dept. of Geriatric Medicine, Faculty of Medicine, Kyoto University, Instructor, 医学部, 助手 (30231690)
NAGANO Yutaka Dept. of Geriatric Medicine, Faculty of Medicine, Kyoto University, Instructor, 医学部, 助手 (80228048)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Oxidized LDL / Oxidized HDL / Acetyl LDL receptor / Oxidized LDL receptor / Macrophage / Kuffer cell / MCP-1 |
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| Research Abstract |
We have reported that mouse peritoneal macrophages have three of receptors for modified LDL(acetyl and oxidized LDL)(BBRC 1989 159p.1375 Arai et al). In current study,the characteristics of modified LDL receptors in rabbit peritoneal macrophages and Kupffer cells were examined. Cross competition analysis of the degradation assay between acetyl and oxidized LDL indicated that rabbit macrophages have two kinds of modified LDL receptors;one is specific for acetyl LDL,and the other recognizes both oxidized and acetyl LDL.
On the other hand,rabbit Kupffer cells have receptor which recognizes oxidized LDL specifically. However,specific receptor for acetyl-LDL does not exist in rabbit Kupffer cells
In addition to LDL,we performed oxidative modification of HDL in vitro. This modification resulted in denaturation of apo A-1 on SDS/PAGE and increased the negative charge on agarose gel electrophoresis. When incubated with macrophages-derived foam cells,native HDL caused a marked efflux of cholesteryl ester in the cells. However oxidized HDL showed a lessened effect on the decrease of cholesteryl ester in foam cells. Nevertheless it was shown that HDL from patients treated by probucol,an antioxidant,is hardly oxidized by Cu^<++>. These results indicated that apo A-1 in HDL particles is essential for efflux of cholesteryl ester in the foam cells.
Finally we found that one of the components of oxidized LDL,lyso-phosphatidylcholine,induced the expression of MCP-1 mRNA in endothelial cells. We are now investigating the detail mechanism of this expression.
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[Publications] Tanaka,M.,Jingami,H.,Otani,H.,Cho,M.,Ueda,Y.,Arai,H.,Nagano,Y.,Doi,T.&Kita,T.: "Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesteryl ester contents in rabbit hepatocytes." J.Biol.Chem.
Description
「研究成果報告書概要(和文)」より
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[Publications] Ueda,Y.,Arai,H.,Kawashima,A.,Nagano,Y.Cho,M.,Tanaka,M.&Kita,T.: "Different expression of modified low density lipoprotein receptors in rabbit peritoneal macrophages and kupffer cells." Atherosclerosis.
Description
「研究成果報告書概要(和文)」より
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[Publications] Kita,T.,Yokdoe,M.,Arai,H.,Iiyama,M.,Ueda,Y.,Ueyama,K.&Narumiya,S.: "Cigarette smoke,LDL and cholesteryl ester accumulation in macrophages." Ann.N.Y.Acad.Sci.
Description
「研究成果報告書概要(和文)」より
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[Publications] Nagano,Y.,Nakamura,T.,Matsuzawa,Y.,Cho.,M.,Ueda,Y.&Kita,T.: "Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit--long-term antiatherogenic effect and effects on established plaques." Atherosclerosis. 92. 131-140 (1992)
Description
「研究成果報告書概要(和文)」より
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[Publications] Tanaka,M.,Jingami,H.,Otani,H.,Cho,M.,Ueda,Y.,Arai,h.,nagano,Y.,Doi,T.& Kita,T: "Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesteryl ester contents in rabbit hepatocytes." J.Biol.Chem.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ueda,Y.,Arai,H.,Kawashima,A.,Nagano,Y.Cho,M.,Tanaka,M.& Kita,T.: "Different expression of modified low density lipoprotein receptors in rabbit peritoneal macrophages and kupffer cells." Atherosclerosis.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kita,T.,Yokode,M.,Arai,H.,Iiyama,M.,Ueda,Y.,Ueyama,K.& Narumiya,S: "Cigarette smoke,LDL and cholesteryl ester accumulation in macrophages." Ann.N.Y.Acad.Sci.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nagano,Y.,Nakamura,T.,Matsuzawa,Y.,Cho,M.,Ueda,Y.& Kita,T: "Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit-long-term antiatherogenic effect and effects on established plaques." Atherosclerosis. 92. 131-140 (1992)
Description
「研究成果報告書概要(欧文)」より
