Defective endocytosis of low-density lipoprotein in monensin-resistant mutants of the mouse Balb/3T3 cell line.
Two monensin-resistant clones show similar low-density lipoprotein binding activity but less internalization or degradation of low-density lipoprotein than the parental Balb/3T3 or other resistant clone. Sterol synthesis from radioactive acetate in the resistant mutant, MO-5, is inhibited by more than 70% of control in the presence of tenfold higher amounts of low-density lipoprotein than the dose that inhibits the parental Balb/3T3 to similar level. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity of Balb/3T3 and MO-5 is inhibited by 48% and 27% of control, respectively, in the presence of 10 micrograms/ml of low-density lipoprotein. Colloidal silica gradient centrifugation shows that transport of low-density lipoprotein from the surface membrane to the lysosome is much slower in MO-5 cells than in Balb/3T3 cells. Down regulation of low-density lipoprotein receptors on the cell surface in Balb/3T3 is observed by exposing the cells to 5-15 micrograms/ml low-density lipoprotein, whereas only slight if any down regulation is observed when MO-5 cells are treated with low-density lipoprotein. The altered endocytosis of low-density lipoprotein behaves as a dominant trait in hybrids of MO-5 and THO2-2, a derivative of Balb/3T3 resistant to both ouabain and 6-thioguanine.
D000818:Animals; D002460:Cell Line; D002468:Cell Physiological Phenomena; D002477:Cells / Q000187:drug effects / Q000378:metabolism*; D004351:Drug Resistance; D004705:Endocytosis; D005663:Furans / Q000502:physiology*; D005799:Genes, Dominant; D005808:Genes, Recessive; D006824:Hybridization, Genetic; D008077:Lipoproteins, LDL / Q000276:immunology*; D008148:Lovastatin / Q000031:analogs & derivatives*; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains; D008985:Monensin / Q000502:physiology*; D009154:Mutation; D009281:Naphthalenes / Q000494:pharmacology; D011973:Receptors, LDL / Q000378:metabolism; D013261:Sterols / Q000378:metabolism
D005663:Furans; D008077:Lipoproteins, LDL; D009281:Naphthalenes; D011973:Receptors, LDL; D013261:Sterols; C012258:mevastatin; D008985:Monensin; D008148:Lovastatin