Exposure of rat peritoneal macrophages to acetylated low density lipoprotein results in release of plasma membrane cholesterol. An efficient substrate for esterification by acyl-CoA:cholesterol acyltransferase
| Autor: | Motoaki Shichiri, S Horiuchi, Moritsugu Shinohara, Yoshimasa Morino, Akira Miyazaki |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Radioisotope Dilution Technique Sterol O-acyltransferase Tritium Models Biological Biochemistry Cell Line Substrate Specificity Membrane Lipids chemistry.chemical_compound Lysosome medicine Animals Humans Scavenger receptor Molecular Biology Cells Cultured Cholesterol Macrophages Cell Membrane Substrate (chemistry) Rats Inbred Strains Biological activity Cell Biology Membrane transport Rats Lipoproteins LDL Kinetics medicine.anatomical_structure Membrane chemistry lipids (amino acids peptides and proteins) Sterol O-Acyltransferase |
| Zdroj: | Journal of Biological Chemistry. 267:1603-1608 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(18)45988-1 |
| Popis: | In J774 macrophages and murine macrophages stimulated with acetylated low density lipoprotein (acetyl-LDL), the plasma membrane free cholesterol (FC) became accessible to acyl-CoA:cholesterol acyltransferase (ACAT) as substrate, the result being an accumulation of cholesteryl esters (CE) (Tabas, I., Rosoff, W. J., and Boykow, G. C (1988) J. Biol. Chem. 263, 1266-1272). As the route of delivery of FC to ACAT was not well characterized, we examined this route in the present study. In foam cells derived from rat peritoneal macrophages by preincubation with acetyl-LDL, esterification of the exogenously labeled [3H]FC was low (1.3% of total labeled cholesterol). In contrast, when cells were first labeled with exogenous [3H]FC and then chased with acetyl-LDL, the esterification was more extensive (9.2% of the total labeled cholesterol). During this experiment a significant portion of cellular [3H]FC was released into the medium (up to 33.4% of the total labeled cholesterol). In experiments using a two-compartment chamber in which cells in the lower and upper chambers were separated by filter paper yet the cells in both compartments could communicate without direct contact, [3H]FC released into the medium was biologically active and could serve as an efficient substrate for ACAT. Thus, when acetyl-LDL is not included in culture medium, FC delivery from the macrophage plasma membrane to ACAT is not enhanced, whereas in the presence of acetyl-LDL, plasma membrane FC released and bound to acetyl-LDL may re-enter the cells, possibly through the scavenger receptor. This would provide a significant route for CE synthesis in macrophages. |
| Databáze: | OpenAIRE |
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