title: Effect of glucose-mediated LDL oxidation on the P388D1 macrophage-like cell line.
abstract: Oxidised human low density lipoprotein (LDL) is thought to play a role in the development of atherosclerosis. Recent reports suggest that glucose-derived oxidants are capable of oxidising LDL. In this report, the effect of glucose-mediated oxidation of LDL upon the macrophage like cell line, P388D(1), was examined. Glucose-mediated oxidation of LDL was assessed by changes in the electrophoretic mobility of LDL and by analysis of lipid content using gas chromatography. The presence of Cu(II) (0.5 microM) was essential for the oxidation of LDL. The oxidation was potentiated by glucose in a dose- and time-dependent manner. At the concentration of LDL used (1 mg/ml), high concentrations of glucose (up to 500 mM) were required to oxidise LDL. The electrophoretic mobility of LDL correlated with the degree of lipid oxidation; both correlated with an inhibitory effect of oxidised LDL upon P388D(1) DNA synthesis. Diethylenetriaminepentaacetic acid (DETAPAC), a transition metal chelator, and aminoguanidine (AMG), an anti-glycation agent, inhibited the oxidation of LDL and attenuated the effects on DNA synthesis. Thus, glucose can mediate transition metal-dependent oxidation of LDL to a level that can affect P388D(1) cells, a mechanism which might have relevance to accelerated atherosclerosis in diabetic patients.
authors.affiliation: University of Cambridge, Department of Pathology, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Millican
authors.forename: M
authors.initials: M
authors.lastname: Bagga
authors.forename: R
authors.initials: R
authors.lastname: Eddy
authors.forename: M J
authors.initials: MJ
authors.lastname: Mitchinson
authors.forename: J V
authors.initials: JV
authors.lastname: Hunt
mesh_terms: D000818:Animals; D002470:Cell Survival; D002849:Chromatography, Gas; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D007941:Leukemia P388 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D004369:Pentetic Acid / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D007502:Iron Chelating Agents; D008077:Lipoproteins, LDL; D004369:Pentetic Acid; D004247:DNA; D005947:Glucose; C004479:pimagedine