Endotoxins inhibit endocytotic catabolism of low-density lipoproteins in Hep G2 cells.
The effects of endotoxins on the uptake and degradation of low-density lipoproteins in Hep G2, a well-differentiated human hepatoma cell line, were studied. The results showed that incubation of Hep G2 cells with 125I-labeled low-density lipoprotein in the presence of endotoxins caused decreased uptake and degradation of 125I-labeled low-density lipoprotein. The inhibitory effects of endotoxins on the uptake and degradation of 125I-labeled low-density lipoprotein were dose and time dependent. With a monoclonal low-density lipoprotein receptor antibody, it was found that endotoxins interfered with both low-density lipoprotein receptor-mediated and non-low-density lipoprotein receptor-mediated uptake. If, however, the cells were pretreated with endotoxins for 1 or 24 hr and then incubated with new medium without endotoxins, no inhibitory effect on the subsequent uptake and degradation of 125I-labeled low-density lipoprotein occurred. Endotoxins had no toxic effects on Hep G2 cells as judged by [3H]thymidine incorporation and by determination of cell growth. Also, endotoxins did not under our experimental conditions induce oxidative modification of low-density lipoprotein. Furthermore, reisolated low-density lipoprotein that had previously been incubated with endotoxin was catabolized to a lower extent by Hep G2 cells than was control low-density lipoprotein. We speculate that the inhibitory effect of endotoxins on cellular low-density lipoprotein catabolism is due to the formation of endotoxin-low-density lipoprotein complexes, which interfere with the binding of low-density lipoprotein to the cell surface.
Liao
W
W
Department of Internal Medicine, Lund University, Malmö General Hospital, Sweden.
Florén
C H
CH
D001692:Biological Transport; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects*; D004731:Endotoxins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008113:Liver Neoplasms; D011485:Protein Binding; D011973:Receptors, LDL / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
D004731:Endotoxins; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D013936:Thymidine