Binding and intracellular fate of beta-very low density lipoprotein in isolated rat liver parenchymal cells.
Binding of rabbit 125I-tyramine-cellobiose-beta-very low density lipoprotein (125ITC-beta-VLDL) was saturable both in suspended and cultured rat liver parenchymal cells, and in isolated rat liver membrane fractions. The specific binding had KD values ranging from 8 to 10 micrograms/ml. At 37 degrees C beta-VLDL was internalized and degraded in parenchymal cells in culture, but only negligible degradation was measured in suspended cells. In cultured cells the degradation was inhibited by lysosomal and microtubular inhibitors, these agents had no effects in suspended cells. Studies of release suggested internalization in suspended cells and subcellular fractionation experiments confirmed that internalized 125ITC-beta-VLDL reached the lysosomal compartment in cultured cells, but not in suspended cells. Since lactosylated (lac-) beta-VLDL was taken up and degraded efficiently by suspended cells, these cells are not in general unable to transport large lipoprotein particles to the lysosomes. We believe that beta-VLDL does not dissociate from the receptor in the endosomes and therefore is retroendocytosed to the plasma membrane. In isolated parenchymal cells the beta-VLDL binding site is supposedly different from the methylamine-activated-alpha 2-macroglobulin (ma-alpha 2M) binding site, since; 1) Excess beta-VLDL did not reduce ma-alpha 2M binding; 2) In suspended parenchymal cells ma-alpha 2M was readily degraded, whereas beta-VLDL was not degraded and 3) The binding of beta-VLDL was not Ca+(+)-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Gudmundsen
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Universitetet i Oslo, Biologisk Institutt, Avdeling for Molekylaer Celle Biologi, Blindern, Oslo, Norge.
Tjelle
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Berg
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D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008744:Methylamines; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; C027451:methylamine