Immunolocalization of acyl-coenzyme A:cholesterol O-acyltransferase in macrophages.

The Journal of Biological Chemistry
N KhelefI Tabas

Abstract

Macrophages in atherosclerotic lesions accumulate large amounts of cholesteryl-fatty acyl esters ("foam cell" formation) through the intracellular esterification of cholesterol by acyl-coenzyme A:cholesterol O-acyltransferase (ACAT). In this study, we sought to determine the subcellular localization of ACAT in macrophages. Using mouse peritoneal macrophages and immunofluorescence microscopy, we found that a major portion of ACAT was in a dense reticular cytoplasmic network and in the nuclear membrane that colocalized with the luminal endoplasmic reticulum marker protein-disulfide isomerase (PDI) and that was in a similar distribution as the membrane-bound endoplasmic reticulum marker ribophorin. Remarkably, another portion of the macrophage ACAT pattern did not overlap with PDI or ribophorin, but was found in as yet unidentified cytoplasmic structures that were juxtaposed to the nucleus. Compartments containing labeled beta-very low density lipoprotein, an atherogenic lipoprotein, did not overlap with the ACAT label, but rather were embedded in the dense reticular network of ACAT. Furthermore, cell-surface biotinylation experiments revealed that freshly harvested, non-attached macrophages, but not those attached to tissue cultu...Continue Reading

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Citations

Dec 16, 1998·Trends in Biochemical Sciences·J E Vance
Dec 9, 2000·Biochimica Et Biophysica Acta·K F BuhmanR V Farese
Dec 9, 2000·Biochimica Et Biophysica Acta·I Tabas
Feb 15, 2000·European Journal of Biochemistry·D ZweytickG Daum
Jan 20, 2005·The Journal of Biological Chemistry·Yan WangAxel Nohturfft
May 16, 2001·Current Opinion in Lipidology·T Y ChangA Miyazaki
Mar 5, 2014·The Journal of Cell Biology·Albert PolRobert G Parton
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Apr 7, 2010·Progress in Lipid Research·Sonia GulatiStephen L Sturley
Dec 17, 2016·Science China. Life Sciences·Jinhai Yu, Peng Li
Jul 25, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·N KhelefF R Maxfield
Aug 31, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Allan D SnidermanRobert S Kiss
May 6, 2003·The Journal of Pharmacology and Experimental Therapeutics·Teruo Hayashi, Tsung-Ping Su
Mar 6, 1999·The Journal of Biological Chemistry·G D LukerD Piwnica-Worms
Aug 19, 2000·The Journal of Biological Chemistry·D L BrasaemleC Londos
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Jul 30, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sonia GulatiStephen L Sturley
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Sep 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Karina Cristina GiannottiCatarina Teixeira

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