Cholesteryl Ester Hydrolase Activity is Abolished in HSL-/- Macrophages but Unchanged in Macrophages Lacking KIAA1363

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2010 Jul 14

PMID 20625037

Citations 30

Authors

Marlene Buchebner

Thomas Pfeifer

Nora Rathke

Prakash G Chandak

Achim Lass

Renate Schreiber

Adelheid Kratzer

Robert Zimmermann

Wolfgang Sattler

Harald Koefeler

Eleonore Frohlich

Gerhard M Kostner

Ruth Birner-Gruenberger

Kyle P Chiang

Guenter Haemmerle

Rudolf Zechner

Sanja Levak-Frank

Benjamin Cravatt

Dagmar Kratky

Affiliations

Soon will be listed here.

Abstract

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, hormone-sensitive 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.

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