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SHR Neuro Krebs Kardio Lipid

Buchebner, M; Pfeifer, T; Rathke, N; Chandak, PG; Lass, A; Schreiber, R; Kratzer, A; Zimmermann, R; Sattler, W; Koefeler, H; Froehlich, E; Kostner, GM; Birner-Gruenberger, R; Chiang, KP; Haemmerle, G; Zechner, R; Levak-Frank, S; Cravatt, BF; Kratky, D.
Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363.
J Lipid Res. 2010; 51(10): 2896-2908. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Aflaki Elma
Birner-Grünberger Ruth
Buchebner Marlene
Chandak Prakash Gopal Das
Fröhlich Eleonore
Köfeler Harald
Kostner Gerhard
Kratky Dagmar
Levak Sanja
Sattler Wolfgang
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Number of Figures: 8
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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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Atherosclerosis - genetics
COS Cells -
Cercopithecus aethiops -
Cholesterol Esters - metabolism
Diglycerides - metabolism
Hydrolysis -
Macrophages - enzymology
Mice -
Mice, Inbred Strains -
Microscopy, Fluorescence -
Serine Proteases - genetics
Sterol Esterase - genetics
Transfection -

Find related publications in this database (Keywords)
2-acetyl monoalkylglycerol ether hydrolase
cholesterol metabolism
lipase
lipids
triacylglycerol
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