CARBON DISULFIDE-INDUCED MODIFICATION AND CYTOTOXICITY OF LOW-DENSITYLIPOPROTEINS

The secondary oxidation of biologically modified low-density lipoprote ins (LDL) was demonstrated to contribute to the cytotoxicity and there by to the atherogenicity of modified lipoproteins. Previously we have shown that chemical modification of LDL by carbon disulfide (CS2) mimi cked the naturally occurring process of LDL modification. In the prese nt study the cytotoxicity of CS2-modified LDL and their susceptibility to the secondary oxidative modification was investigated. The cytotox icity of CS2-modified LDL did not significantly exceed that of native LDL. However, the Cu2+-oxidized form of CS2-modified LDL revealed to b e more cytotoxic than oxidized native LDL. Oxidized CS2-modified LDL p resented with altered physicochemical properties including derivatizat ion of protein amino and -SH groups, increased negative charge, and el ectrophoretic mobility which exceeded that of oxidized native LDL. The secondary oxidative modification of CS2-modified LDL involved the pro cess of Cu2+ binding to CS2-derived dithiocarbamate -SH groups followe d by covalent modification of -SH groups by products of lipid peroxida tion. Taken together, these finding suggest that secondary oxidation o f CS?-modified LDL may contribute to the atherogenic effect of the chr onic occupational exposure to CSI. Copyright (C) 1996 Elsevier Science Ltd.