title: Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed.
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 PPARδ 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.
authors: Department of Medical Biosciences, Physiological Chemistry Umeå University, SE-901 87 Umeå, Sweden.
authors: Elena
authors: E
authors: Makoveichuk
authors: Valentina
authors: V
authors: Sukonina
authors: Olessia
authors: O
authors: Kroupa
authors: Petra
authors: P
authors: Thulin
authors: Ewa
authors: E
authors: Ehrenborg
authors: Thomas
authors: T
authors: Olivecrona
authors: Gunilla
authors: G
authors: Olivecrona
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D047494:PPAR delta / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C425931:GW 501516; D047494:PPAR delta; D013844:Thiazoles; D003609:Dactinomycin; C548261:LPL protein, human; D008071:Lipoprotein Lipase