Different effects of the glucosidase inhibitors 1-deoxynojirimycin, N-methyl-1-deoxynojirimycin and castanospermine on the glycosylation of rat alpha 1-proteinase inhibitor and alpha 1-acid glycoprotein.
The glucosidase inhibitors 1-deoxynojirimycin, N-methyl-1-deoxynojirimycin and castanospermine were used to inhibit oligosaccharide processing in primary cultures of rat hepatocytes. Their effect on the glycosylation of alpha 1-proteinase inhibitor (alpha 1PI) and alpha 1-acid glycoprotein (alpha 1AGP) was studied. Of the three glucosidase inhibitors examined, 1-deoxynojirimycin inhibited not only oligosaccharide trimming but also glycosylation de novo of newly synthesized proteins, resulting in the formation of alpha 1PI with two and three (normally carrying three) and alpha 1AGP with two to five (normally carrying six) oligosaccharide side chains. In the presence of the glucosidase inhibitors, glucosylated high-mannose-type oligosaccharides accumulated. Whereas most of the endoglucosaminidase-H-sensitive oligosaccharides formed in the presence of 1-deoxynojirimycin contained only one glucose residue, N-methyl-1-deoxynojirimycin and castanospermine led mainly to the formation of oligosaccharides with three glucose residues. None of the three glucosidase inhibitors completely prevented the formation of complex-type oligosaccharides. Thus, in their presence, alpha 1PI and alpha 1AGP with a mixture of both high-mannose and complex-type oligosaccharides were secreted.
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D006031:Glycosylation; D007212:Indolizines; D008099:Liver / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D009961:Orosomucoid / Q000378:metabolism*; D051381:Rats; D000515:alpha 1-Antitrypsin; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D000470:Alkaloids; D001798:Blood Proteins; D005944:Glucosamine; D005959:Glucosidases; D007212:Indolizines; D009844:Oligosaccharides; D009961:Orosomucoid; D000515:alpha 1-Antitrypsin; C037806:castanospermine; D054836:Indolizidines; C033424:N-methyldeoxynojirimycin