monensin and mevastatin

Topics: Animals; Carbohydrate Sequence; Cell Line; Hyperlipoproteinemia Type II; Lovastatin; Molecular Sequence Data; Monensin; Mutation; Receptors, LDL

Topics: Alkylating Agents; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aphidicolin; Camptothecin; Cell Separation; Drug Resistance; Etoposide; Humans; Hydroxamic Acids; Lovastatin; Monensin; Nucleic Acids; Teniposide; Toxins, Biological; Tunicamycin

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.

Topics: Animals; Cell Line; Cell Physiological Phenomena; Cells; Drug Resistance; Endocytosis; Furans; Genes, Dominant; Genes, Recessive; Hybridization, Genetic; Lipoproteins, LDL; Lovastatin; Mice; Mice, Inbred Strains; Monensin; Mutation; Naphthalenes; Receptors, LDL; Sterols