The oxidation of low-density lipoprotein (LDL) is implicated in atherosclerosis. Lipids and oxidized lipids were analysed by gas chromatography and gas chromatography-mass spectrometry in human LDL incubated with mouse peritoneal macrophages (MPM) or copper (II) sulphate in Ham's F-10 medium or medium alone (control). MPM-modification and copper-catalysed oxidation of LDL resulted in the formation of oxysterols, mainly cholest-5-en-3 beta,7 beta-diol (7 beta-OH-CHOL); 7%-19% of the initial cholesterol was converted to 7 beta-OH-CHOL in 24 h. 7 beta-OH-CHOL levels in control LDL were very low. The increase in 7 beta-OH-CHOL in MPM and copper-oxidized LDL was accompanied by decreases in linoleate and arachidonate and increases in the electrophoretic mobility and degradation of LDL protein by ‘target’ macrophages. The concerted occurrence of these processes and their similarity in both MPM-modification and copper-catalysed oxidation of LDL were suggested by the highly significant cross-correlations. The fall in polyunsaturated fatty acid (PUFA) was accompanied by a directly proportional increase in electrophoretic mobility of the LDL. Production of 7 beta-OH-CHOL and protein degradation by macrophages showed modest elevations during the initial steep fall in PUFA, and showed their greatest increases as the levels of PUFA slowly approached zero. The levels of 7 beta-OH-CHOL and the degradation of LDL by macrophages were directly proportional. The degradation of LDL by macrophages increased rapidly as the electrophoretic mobility of LDL was slowly approaching its maximum level.
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December 1994
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Research Article|
December 01 1994
Production of oxidized lipids during modification of low-density lipoprotein by macrophages or copper
K L Carpenter;
K L Carpenter
*Division of Cellular Pathology, University of Cambridge, Department of Pathology, Cambridge CB2 1QP, U.K.
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G M Wilkins;
G M Wilkins
†Department of Biochemistry and Physiology, University of Reading, Whiteknights, PO Box 228, Reading, Berks. RG6 2AJ, U.K.
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B Fussell;
B Fussell
‡†E.P.S.R.C. Mass Spectrometry Service Centre, Department of Chemistry, University of Wales, Swansea SA2 8PP, U.K.
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J A Ballantine;
J A Ballantine
‡†E.P.S.R.C. Mass Spectrometry Service Centre, Department of Chemistry, University of Wales, Swansea SA2 8PP, U.K.
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S E Taylor;
S E Taylor
*Division of Cellular Pathology, University of Cambridge, Department of Pathology, Cambridge CB2 1QP, U.K.
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M J Mitchinson;
M J Mitchinson
*Division of Cellular Pathology, University of Cambridge, Department of Pathology, Cambridge CB2 1QP, U.K.
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D S Leake
D S Leake
*Division of Cellular Pathology, University of Cambridge, Department of Pathology, Cambridge CB2 1QP, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1994 The Biochemical Society, London
1994
Biochem J (1994) 304 (2): 625–633.
Citation
K L Carpenter, G M Wilkins, B Fussell, J A Ballantine, S E Taylor, M J Mitchinson, D S Leake; Production of oxidized lipids during modification of low-density lipoprotein by macrophages or copper. Biochem J 1 December 1994; 304 (2): 625–633. doi: https://doi.org/10.1042/bj3040625
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