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Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2012 Aug 24; Vol. 425 (2), pp. 138-43. Date of Electronic Publication: 2012 Jul 20. - Publication Year :
- 2012
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Abstract
- Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins causing release of fatty acids for metabolic purposes in muscles and adipose tissue. LPL in macrophages in the artery wall may, however, promote foam cell formation and atherosclerosis. Angiopoietin-like protein (ANGPTL) 4 inactivates LPL and ANGPTL4 expression is controlled by peroxisome proliferator-activated receptors (PPAR). The mechanisms for inactivation of LPL by ANGPTL4 was studied in THP-1 macrophages where active LPL is associated with cell surfaces in a heparin-releasable form, while LPL in the culture medium is mostly inactive. The PPARĪ“ agonist GW501516 had no effect on LPL mRNA, but increased ANGPTL4 mRNA and caused a marked reduction of the heparin-releasable LPL activity concomitantly with accumulation of inactive, monomeric LPL in the medium. Intracellular ANGPTL4 was monomeric, while dimers and tetramers of ANGPTL4 were present in the heparin-releasable fraction and medium. GW501516 caused an increase in the amount of ANGPTL4 oligomers on the cell surface that paralleled the decrease in LPL activity. Actinomycin D blocked the effects of GW501516 on ANGPTL4 oligomer formation and prevented the inactivation of LPL. Antibodies against ANGPTL4 interfered with the inactivation of LPL. We conclude that inactivation of LPL in THP-1 macrophages primarily occurs on the cell surface where oligomers of ANGPTL4 are formed.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Angiopoietin-Like Protein 4
Cell Line
Cell Membrane enzymology
Cell Membrane metabolism
Dactinomycin pharmacology
Humans
Lipoprotein Lipase antagonists & inhibitors
Macrophages enzymology
Monocytes cytology
Monocytes metabolism
PPAR delta antagonists & inhibitors
Thiazoles pharmacology
Angiopoietins metabolism
Lipoprotein Lipase metabolism
Macrophages metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 425
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 22820186
- Full Text :
- https://doi.org/10.1016/j.bbrc.2012.07.048