Effect of glucose-mediated LDL oxidation on the P388D1 macrophage-like cell line

• Published in: Atherosclerosis Vol. 129; no. 1; pp. 17 - 25
• Main Authors: Millican, Stephanie A, Bagga, Meena, Eddy, Rachel, Mitchinson, Malcolm J, Hunt, James V
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 28.02.1997; Elsevier
• Subjects: Animals; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Survival; Chromatography, Gas; DNA - antagonists & inhibitors; DNA - biosynthesis; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Glucose; Glucose - pharmacology; Guanidines - pharmacology; Humans; Iron Chelating Agents - pharmacology; Leukemia P388 - metabolism; Lipoproteins, LDL - drug effects; Lipoproteins, LDL - metabolism; Low density lipoprotein; Macrophage; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Mice; Oxidation; Oxidation-Reduction - drug effects; Pentetic Acid - pharmacology; Tumor Cells, Cultured; Oxidation; Glucose; Low density lipoprotein; Atherosclerosis; Macrophage; Human; Cell culture; Rodentia; Cardiovascular disease; Exploration; Vascular disease; Lipoprotein LDL; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(96)06004-2

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 μM) 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.