5-hydroxy-6-8-11-14-eicosatetraenoic-acid and Lymphoma--Large-B-Cell--Diffuse

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.

Topics: 5-Lipoxygenase-Activating Proteins; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Blotting, Northern; Carrier Proteins; Cell Line; Enzyme Activation; Gene Expression; Humans; Hydroxyeicosatetraenoic Acids; Kinetics; Leukemia; Lipoproteins, LDL; Lymphoma, Large B-Cell, Diffuse; Malondialdehyde; Membrane Proteins; Oxidation-Reduction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Neoplasm; Transcription, Genetic; Tumor Cells, Cultured