Inhibition by swainsonine of the degradation of endocytosed glycoproteins in isolated rat liver parenchymal cells.
Swainsonine, an alpha-mannosidase inhibitor found in the Australian plant Swainsona canescens and in spotted locoweed, was tested for its effect on the degradation of endocytosed proteins in rat liver cells. The compound inhibited the release of proteolytically derived breakdown products from endocytosed glycoproteins but not from nonglycoproteins. Fifty per cent inhibition of the degradation of 125I-asialofetuin occurred at a concentration of swainsonine in the medium of 6 X 10(-7) M. In the presence of the inhibitor, there was an increased cellular accumulation of the glycoproteins corresponding quantitatively to the decreased degradation, so that total uptake was the same in the presence or absence of the inhibitor. The excess 125I-labeled material which accumulated within cells under these conditions was found entirely in the lysosomal peak on Percoll density gradient centrifugation and migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a mobility indistinguishable from that of the original material. Thus, the inhibition of breakdown occurs prior to any conversion of the protein to intermediates of detectably smaller size. In contrast to the results with swainsonine, degradation of both glycoproteins and nonglycoproteins was inhibited by chloroquine and by 3-methyladenine. The findings with 3-methyladenine are in conflict with earlier reports in the literature on the effect of this compound on degradation of endocytosed proteins.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001212:Asialoglycoproteins; D004705:Endocytosis / Q000187:drug effects*; D060748:Fetuins; D006023:Glycoproteins / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D017026:Swainsonine; D000509:alpha-Fetoproteins / Q000378:metabolism
D000470:Alkaloids; D001212:Asialoglycoproteins; D060748:Fetuins; D006023:Glycoproteins; D000509:alpha-Fetoproteins; C017029:asialofetuin; D017026:Swainsonine