Cell lipid metabolism modulators 2-bromopalmitate, D609, monensin, U18666A and probucol shift discoidal HDL formation to the smaller-sized particles: implications for the mechanism of HDL assembly
| Autor: | Fiona M. La, Michael C. Phillips, Angel X. Xiao, Duyen Quach, Chongren Tang, Daniel J. Rader, Cecilia Vitali, Nicholas N. Lyssenko, John S. Millar |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Bridged-Ring Compounds Apolipoprotein B Probucol Palmitates Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Tangier disease Thiocarbamates Cell Line Tumor medicine Animals Humans Monensin Particle Size Molecular Biology Phospholipids chemistry.chemical_classification 030102 biochemistry & molecular biology biology Apolipoprotein A-I Cholesterol Macrophages Cell Membrane nutritional and metabolic diseases Thiones Lipid metabolism Cell Biology medicine.disease Lipid Metabolism Norbornanes 030104 developmental biology RAW 264.7 Cells Biochemistry chemistry ABCA1 biology.protein Fatty Acids Unsaturated lipids (amino acids peptides and proteins) Androstenes Lipoproteins HDL medicine.drug Polyunsaturated fatty acid Lipoprotein ATP Binding Cassette Transporter 1 |
| Zdroj: | Biochimica et biophysica acta. 1861(12 Pt) |
| ISSN: | 0006-3002 |
| Popis: | ATP-binding cassette transporter A1 (ABCA1) mediates formation of disc-shaped high-density lipoprotein (HDL) from cell lipid and lipid-free apolipoprotein A-I (apo A-I). Discoidal HDL particles are heterogeneous in physicochemical characteristics for reasons that are understood incompletely. Discoidal lipoprotein particles similar in characteristics and heterogeneity to cell-formed discoidal HDL can be reconstituted from purified lipids and apo A-I by cell-free, physicochemical methods. The heterogeneity of reconstituted HDL (rHDL) is sensitive to the lipid composition of the starting lipid/apo A-I mixture. To determine whether the heterogeneity of cell-formed HDL is similarly sensitive to changes in cell lipids, we investigated four compounds that have well-established effects on cell lipid metabolism and ABCA1-mediated cell cholesterol efflux. 2-Bromopalmitate, D609, monensin and U18666A decreased formation of the larger-sized, but dramatically increased formation of the smaller-sized HDL. 2-Bromopalmitate did not appear to affect ABCA1 activity, subcellular localization or oligomerization, but induced dissolution of the cholesterol-phospholipid complexes in the plasma membrane. Arachidonic and linoleic acids shifted HDL formation to the smaller-sized species. Tangier disease mutations and inhibitors of ABCA1 activity wheat germ agglutinin and AG 490 reduced formation of both larger-sized and smaller-sized HDL. The effect of probucol was similar to the effect of 2-bromopalmitate. Taking rHDL formation as a paradigm, we propose that ABCA1 mutations and activity inhibitors reduce the amount of cell lipid available for HDL formation, and the compounds in the 2-bromopalmitate group and the polyunsaturated fatty acids change cell lipid composition from one that favors formation of the larger-sized HDL particles to one that favors formation of the smaller-sized species. |
| Databáze: | OpenAIRE |
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