Carbon disulfide-induced modification and cytotoxicity of low-density lipoproteins

The secondary oxidation of biologically modified low-density lipoproteins (LDL) was demonstrated to contribute to the cytotoxicity and thereby to the atherogenicity of modified lipoproteins. Previously we have shown that chemical modification of LDL by carbon disulfide (CS(2)) mimicked the naturally occurring process of LDL modification. In the present study the cytotoxicity of CS(2)-modified LDL and their susceptibility to the secondary oxidative modification was investigated. The cytotoxicity of CS(2)-modified LDL did not significantly exceed that of native LDL. However, the Cu(2+) -oxidized form of CS(2)-modified LDL revealed to be more cytotoxic than oxidized native LDL. Oxidized CS(2)-modified LDL presented with altered physicochemical properties including derivatization of protein amino and - SH groups, increased negative charge, and electrophoretic mobility which exceeded that of oxidized native LDL. The secondary oxidative modification of CS(2)-modified LDL involved the process of Cu(2+) binding to CS(2)-derived dithiocarbamate -SH groups followed by covalent modification of - SH groups by products of lipid peroxidation. Taken together, these finding suggest that secondary oxidation of CS(2)-modified LDL may contribute to the atherogenic effect of the chronic occupational exposure to CS(2).