Characterization of a very-low-density lipoprotein (VLDL)-associated cytotoxic factor

Abstract

Summary.-A VLDL-associated cytotoxic factor was isolated from sera of pregnant rats and characterized. The inhibitory effect of this factor on the macromolecular synthesis of rat prostate adenocarcinoma cells (PA-III) was also examined. VLDL (Sf 20-4C0) was subfractionated by differential ultracentrifugal flotation and the Sf 100-400 fraction was associated with most of the oncolytic activity. Chemical analysis of serum VLDL at various stages of pregnancy indicated that the 4 major constituents of VLDL (protein, triglyceride, cholesterol, and phospholipid), and the cytotoxic titre, were increased significantly before parturition and restored to normal levels by 24 h post partum. The delipidation of lyophilized VLDL by n-heptane suggested that the cytotoxic component was associated with the neutral lipid core of VLDL.Kinetic studies of colony inhibition and the incorporation of radioactive thymidine and leucine into 10% TCA precipitates of PA-III cells showed that VLDL induced irreparable cellular damage during the initial 15 h of incubation. The cytotoxic activity of VLDL was not due to the association with PGF2a,

Toxicity of oxidized low‐density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle

“…Circumstantial evidence suggests that o-LDL may play a role in vivo: (1) Diabetic patients have been shown to have increased thiobarbituric acid reactivity associated with their plasma lipoproteins (Nishigaki et al, 1981;Delamothe et al, 19811, and oxidized lipoproteins have also been identified in other pathological circumstances (Yagi, 1984). (2) Lipoproteins isolated from particular animal and human populations have been shown to be toxic to cells in culture (Chan andPollard, 1981, Gianturco et al, 1980), including lipoprotein fractions from diabetic rats (Arbogast et al, 1982). (3) The ability to oxidize extracellular lipoproteins in vivo exists since certain leukocyte populations are believed to produce free radicals in vivo (Fantone and Ward, 1982), and the oxidation of LDL which renders it toxic is known to be a free-radical-mediated process (Morel et al, 1983a).…”