Oxidized low density lipoprotein increases U937 cell 5-lipoxygenase activity: induction of 5-lipoxygenase activating protein.
This study examines the effects of oxidized low density lipoprotein (ox-LDL) on mononuclear cell arachidonic acid (AA) metabolism. U937 and HL60 cells, employed as models for mononuclear cells and promyelocytic cells, respectively, were exposed to ox-LDL (20 micrograms protein/ml) for 24 hours. HPLC analysis of 1-14C-AA metabolites indicates that ox-LDL increases U937 and HL60 cell production of 15-hydroxyeicosatetraenoic acid (15-HETE) and 5-hydroxyeicosatetraenoic acid (5-HETE). Northern analysis indicates that ox-LDL increases U937 cell FLAP transcript levels 10-times control levels but did not appear to alter 5-lipoxygenase (5-LO) mRNA levels. In contrast, ox-LDL increases HL60 cell transcript levels for FLAP and 5-LO 1.5 times and 10 times control levels, respectively. Thus, we propose that ox-LDL plays an important role in the up-regulation of the 5-LO pathway in mononuclear cells. Such activation may explain, in part, the mechanisms by which ox-LDL promotes atherogenesis.
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Department of Experimental Pathology, New York Medical College, Valhalla 10595.
Pritchard
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D058927:5-Lipoxygenase-Activating Proteins; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007700:Kinetics; D007938:Leukemia; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D016403:Lymphoma, Large B-Cell, Diffuse; D008315:Malondialdehyde; D008565:Membrane Proteins / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D012334:RNA, Neoplasm / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D006893:Hydroxyeicosatetraenoic Acids; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012334:RNA, Neoplasm; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D008315:Malondialdehyde; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001094:Arachidonate 5-Lipoxygenase