Carbon disulfide modification and impaired catabolism of low density lipoprotein

Carbon disulfide interacts in vitro with low density lipoprotein (LDL), resulting in an increased electrophoretic mobility of the particle, due to a decrease in free amino groups of apolipoprotein B-100. The processing of carbon disulfide-modified LDL through the apo B/E receptor pathway of cultured human fibroblasts is decreased as compared to that of native LDL, depending on the level of modification. Carbon disulfide-modified LDL is recognized and degraded by the scavenger pathway of macrophages, but to a lesser extent than acetylated LDL. Carbon disulfide modification decreases the ability of the LDL to down-regulate sterol synthesis and to stimulate cholesterol esterification in fibroblasts. Carbon disulfide-modified LDL markedly stimulates cholesteryl ester formation in macrophages, albeit to a lesser extent than acetylated LDL. These results indicate that after carbon disulfide modification the LDL catabolism is shifted to the scavenger pathway, and are consistent with the fact that carbon disulfide intoxication accelerates the appearance of atherosclerotic lesions.