Sterol 27-hydroxylase- and apoAI/phospholipid-mediated efflux of cholesterol from cholesterol-laden macrophages: evidence for an inverse relation between the two mechanisms
| Autor: | Ulf Diczfalusy, Jan Nilsson, Jan Westman, Ingemar Björkhem, Bengt Kallin |
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| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Apolipoprotein B medicine.medical_treatment Phospholipid Biology Steroid chemistry.chemical_compound High-density lipoprotein Cytochrome P-450 Enzyme System Internal medicine medicine Humans Cells Cultured Phospholipids chemistry.chemical_classification Apolipoprotein A-I Cholesterol Macrophages Reverse cholesterol transport Biological Transport Hydroxycholesterols Endocrinology Enzyme chemistry Biochemistry Culture Media Conditioned Steroid Hydroxylases biology.protein Cholestanetriol 26-Monooxygenase lipids (amino acids peptides and proteins) Efflux Cardiology and Cardiovascular Medicine |
| Zdroj: | Karolinska Institutet Scopus-Elsevier |
| ISSN: | 1079-5642 |
| Popis: | Abstract —Cholesterol-laden, human monocyte–derived macrophages were found to contain 27-hydroxycholesterol in proportion to their content of cholesterol ester. In accordance with previous work with human lung alveolar macrophages, there was a significant efflux of 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid from the cultured cells. The efflux of 27-hydroxycholesterol was proportional to the cellular content of this steroid. Incubation of cholesterol-laden macrophages with reconstituted discoidal complexes made from apolipoprotein A-I and phospholipids resulted in a decrease in total cellular cholesterol, an increase in the efflux of free cholesterol, and a concomitant decrease in the total production and efflux of 27-oxygenated steroids, in particular, 3β-hydroxy-5-cholestenoic acid. Reconstituted discoidal complexes with the Milano variant of apolipoprotein A-I gave virtually identical results, whereas high density lipoprotein was less efficient. These results suggest that cultured cholesterol-laden cells can export some of their excess cholesterol in the form of 27-hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid, and free cholesterol. In the presence of exogenous cholesterol acceptors, export of free cholesterol becomes more effective, resulting in less cholesterol exported via the 27-hydroxylase pathway. The balance between the two mechanisms for removal of cholesterol from macrophages may be of importance for formation of foam cells and development of atherosclerosis. |
| Databáze: | OpenAIRE |
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