Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363

被引：48

作者：

Buchebner, Marlene ^{[1
]}

Pfeifer, Thomas ^{[1
]}

Rathke, Nora ^{[1
]}

Chandak, Prakash G. ^{[1
]}

Lass, Achim ^{[4
]}

Schreiber, Renate ^{[4
]}

Kratzer, Adelheid ^{[1
]}

Zimmermann, Robert ^{[4
]}

Sattler, Wolfgang ^{[1
]}

Koefeler, Harald ^{[2
,3
]}

Froehlich, Eleonore ^{[2
,3
]}

Kostner, Gerhard M. ^{[1
]}

Birner-Gruenberger, Ruth ^{[2
,3
]}

Chiang, Kyle P. ^{[5
,6
]}

Haemmerle, Guenter ^{[4
]}

Zechner, Rudolf ^{[4
]}

Levak-Frank, Sanja ^{[1
]}

Cravatt, Benjamin ^{[5
,6
]}

Kratky, Dagmar ^{[1
]}

机构：

[1] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria

[2] Med Univ Graz, Ctr Mol Med, Graz, Austria

[3] Med Univ Graz, Med Res Ctr, Graz, Austria

[4] Graz Univ, Inst Mol Biosci, Graz, Austria

[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[6] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

来源：

JOURNAL OF LIPID RESEARCH | 2010年 / 51卷 / 10期

基金：

奥地利科学基金会; 美国国家卫生研究院;

关键词：

2-acetyl monoalkylglycerol ether hydrolase; cholesterol metabolism; lipase; lipids; triacylglycerol; HORMONE-SENSITIVE LIPASE; LOW-DENSITY-LIPOPROTEIN; ADIPOSE-TISSUE; FOAM CELLS; ENZYME; HYDROLYSIS; METABOLISM; MICE; OVEREXPRESSION; IDENTIFICATION;

D O I：

10.1194/jlr.M004259

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cholesteryl ester (CE) accumulation in macrophages represents a crucial event during foam cell formation, a hallmark of atherogenesis. Here we investigated the role of two previously described CE hydrolases, hormonesensitive lipase (HSL) and KIAA1363, in macrophage CE hydrolysis. HSL and KIAA1363 exhibited marked differences in their abilities to hydrolyze CE, triacylglycerol (TG), diacylglycerol (DG), and 2-acetyl monoalkylglycerol ether (AcMAGE), a precursor for biosynthesis of platelet-activating factor (PAF). HSL efficiently cleaved all four substrates, whereas KIAA1363 hydrolyzed only AcMAGE. This contradicts previous studies suggesting that KIAA1363 is a neutral CE hydrolase. Macrophages of KIAA1363(-/-) and wild-type mice exhibited identical neutral CE hydrolase activity, which was almost abolished in tissues and macrophages of HSL-/- mice. Conversely, AcMAGE hydrolase activity was diminished in macrophages and some tissues of KIAA1363(-/-) but unchanged in HSL-/- mice. CE turnover was unaffected in macrophages lacking KIAA1363 and HSL, whereas cAMP-dependent cholesterol efflux was influenced by HSL but not by KIAA1363. Despite decreased CE hydrolase activities, HSL-/- macrophages exhibited CE accumulation similar to wild-type (WT) macrophages. We conclude that additional enzymes must exist that cooperate with HSL to regulate CE levels in macrophages. KIAA1363 affects AcMAGE hydrolase activity but is of minor importance as a direct CE hydrolase in macrophages.-Buchebner, M., T. Pfeifer, N. Rathke, P.G. Chandak, A. Lass, R. Schreiber, A. Kratzer, R. Zimmermann, W. Sattler, H. Koefeler, E. Frohlich, G. M. Kostner, R. Birner-Gruenberger, K. P. Chiang, G. Haemmerle, R. Zechner, S. Levak-Frank, B. Cravatt, and D. Kratky. Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363. J. Lipid Res. 2010. 51:2896-2908.

引用

页码：2896 / 2908

页数：13

共 41 条

[1]

DEGRADATION OF CATIONIZED LOW-DENSITY LIPOPROTEIN AND REGULATION OF CHOLESTEROL-METABOLISM IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA FIBROBLASTS [J].