EFFECT OF GLUCOSE-MEDIATED LDL OXIDATION ON THE P388D1 MACROPHAGE-LIKE CELL-LINE

Oxidised human low density lipoprotein (LDL) is thought to play a role in the development of atherosclerosis. Recent reports suggest that gl ucose-derived oxidants are capable of oxidising LDL. In this report, t he effect of glucose-mediated oxidation of LDL upon the macrophage lik e 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 C u(II) (0.5 mu M) was essential for the oxidation of LDL. The oxidation was potentiated by glucose in a dose- and time-dependent manner. At t he concentration of LDL used (1 mg/ml), high concentrations of glucose (up to 500 mM) were required to oxidise LDL. The electrophoretic mobi lity of LDL correlated with the degree of lipid oxidation; both correl ated with an inhibitory effect of oxidised LDL upon P388D(1) DNA synth esis. Diethylenetriaminepentaacetic acid (DETAPAC), a transition metal chelator, and aminoguanidine (AMG), an anti-glycation agent, inhibite d the oxidation of LDL and attenuated the effects on DNA synthesis. Th us, 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. (C) 199 7 Elsevier Science Ireland Ltd.