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
Copyright © 2016 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1861 |
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| Enthalten in: |
Biochimica et biophysica acta - 1861(2016), 12 Pt A vom: 15. Dez., Seite 1968-1979 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Quach, Duyen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.10.2017 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbalip.2016.09.017 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM264730291 |
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| 100 | 1 | |a Quach, Duyen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cell lipid metabolism modulators 2-bromopalmitate, D609, monensin, U18666A and probucol shift discoidal HDL formation to the smaller-sized particles |b implications for the mechanism of HDL assembly |
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| 500 | |a Date Completed 19.10.2017 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HDL heterogeneity | |
| 650 | 4 | |a Inhibitors of ABCA1-mediated cholesterol efflux | |
| 650 | 4 | |a Mechanism of HDL formation | |
| 650 | 4 | |a Reconstituted HDL | |
| 650 | 4 | |a Tangier disease mutations | |
| 650 | 7 | |a ATP Binding Cassette Transporter 1 |2 NLM | |
| 650 | 7 | |a Androstenes |2 NLM | |
| 650 | 7 | |a Apolipoprotein A-I |2 NLM | |
| 650 | 7 | |a Bridged-Ring Compounds |2 NLM | |
| 650 | 7 | |a Fatty Acids, Unsaturated |2 NLM | |
| 650 | 7 | |a Lipoproteins, HDL |2 NLM | |
| 650 | 7 | |a Norbornanes |2 NLM | |
| 650 | 7 | |a Palmitates |2 NLM | |
| 650 | 7 | |a Phospholipids |2 NLM | |
| 650 | 7 | |a Thiocarbamates |2 NLM | |
| 650 | 7 | |a Thiones |2 NLM | |
| 650 | 7 | |a 2-bromopalmitate |2 NLM | |
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| 650 | 7 | |a 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one |2 NLM | |
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| 650 | 7 | |a tricyclodecane-9-yl-xanthogenate |2 NLM | |
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| 650 | 7 | |a Monensin |2 NLM | |
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| 650 | 7 | |a Cholesterol |2 NLM | |
| 650 | 7 | |a 97C5T2UQ7J |2 NLM | |
| 650 | 7 | |a Probucol |2 NLM | |
| 650 | 7 | |a P3CTH044XJ |2 NLM | |
| 700 | 1 | |a Vitali, Cecilia |e verfasserin |4 aut | |
| 700 | 1 | |a La, Fiona M |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Angel X |e verfasserin |4 aut | |
| 700 | 1 | |a Millar, John S |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Chongren |e verfasserin |4 aut | |
| 700 | 1 | |a Rader, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Phillips, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Lyssenko, Nicholas N |e verfasserin |4 aut | |
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