Glutathione (GSH) and the toxicity of oxidised low-density lipoprotein to human monocyte-macrophages

Macrophage death, believed to be an important event in the pathogenesis of human atherosclerosis, can be induced by oxidised low-density lipoprotein ( LDL) in vitro. Supplementation of the culture medium with 5 mM GSH signific antly protected human monocyte-macrophages in vitro against the toxicity of copper-oxidised LDL. Oxidation products of LDL include the aldehyde 4-hydroxynonenal (HNE). We p resent evidence that conjugation of HNE by GSH contributes to this protecti on. In the absence of cells, HPLC analysis showed there were marked reducti ons in the levels of both pure HNE and HNE in copper-oxidised LDL in the pr esence of GSH. However, GSH did not reverse protein modification, as judged by agarose gel electrophoresis, nor did it influence the depletion of poly unsaturated fatty acids, which were assessed using gas chromatography. The possible implications for human atherosclerosis are discussed.