Adiponectin down-regulates acyl-coenzyme A:cholesterol acyltransferase-1 in cultured human monocyte-derived macrophages

被引:78
作者
Furukawa, K
Hori, M
Ouchi, N
Kihara, S
Funahashi, T
Matsuzawa, Y
Miyazaki, A
Nakayama, H
Horiuchi, S [1 ]
机构
[1] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Med Biochem, Kumamoto, Japan
[2] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Molecular Cell Funct, Kumamoto, Japan
[3] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Osaka, Japan
[4] Showa Univ, Sch Med, Dept Biochem, Tokyo, Japan
基金
日本学术振兴会;
关键词
adiponectin; acyl-coenzyme A : cholesterol acyltransferase-1; macrophages; foam cell; atherosclerosis;
D O I
10.1016/j.bbrc.2004.03.123
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acyl-coenzyrne A:cholesterol acyltransferase-1 (ACAT-1) catalyzes the formation of cholesteryl esters (CE) and plays a significant role in formation of macrophage-derived foam cells in atherosclerotic lesions. Adiponectin was reported to play an antiatherogenic role by inhibiting class A scavenger receptor (SR-A) expression in human macrophages. To further clarify its additional property, we examined its effect on ACAT-1 expression using human macrophages. Immunoblot analyses revealed a significant reduction of ACAT-1 protein by a low concentration (1 mug/ml) of adiponectin. The ACAT activity was also decreased in parallel by adiponectin. Northern blot analyses revealed that all four ACAT-1 mRNA transcripts (2.8, 3.6, 4.3, and 7.0 kb) were decreased almost equally by adiponectin. Furthermore, acetyl-LDL-induced CE-accumulation in these macrophages was reduced significantly by this adipocytokine. These results demonstrate the inhibitory effect of adiponectin on ACAT-1 expression, suggesting that adiponectin may play an anti-atherogenic role by down-regulating the expression of ACAT-1 as well as SR-A in human macrophages. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:831 / 836
页数:6
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