Effect of the alpha-glucosidase inhibitor N-hydroxyethyl-1-deoxynojirimycin (Bay m 1099) on the biosynthesis of liver secretory glycoproteins.
The effect of the alpha-glucosidase inhibitor N-hydroxyethyl-1-deoxynojirimycin (Bay m 1099) on the glycosylation and secretion of alpha 1-antitrypsin (three complex type oligosaccharide chains) and of alpha 1-acid glycoprotein (six complex type oligosaccharide chains) was studied in rat hepatocyte primary cultures. In the presence of 4 mM Bay m 1099 the processing of high-mannose to complex type oligosaccharides was partially inhibited leading to the secretion of alpha 1-antitrypsin and alpha 1-acid glycoprotein carrying a mixture of both high-mannose and complex type oligosaccharides. The major part of alpha 1-antitrypsin secreted by Bay m 1099 treated cells still carried two complex type oligosaccharide chains, the majority of alpha 1-acid glycoprotein carried three to five. Despite its effects on protein glycosylation Bay m 1099 did not lead to pronounced changes in the synthesis or secretion of alpha 1-antitrypsin, alpha 1-acid glycoprotein or albumin. At concentrations of Bay m 1099 lower than 0.5 mM no inhibitory effect on oligosaccharide trimming could be observed. After removal of Bay m 1099 from hepatocytes its inhibitory effect on protein glycosylation was immediately reversible.
Ludolph
D
D
Medizinische Klinik, Albert-Ludwigs-Universität, Freiburg, West Germany.
Gross
V
V
Katz
N R
NR
Giffhorn-Katz
S
S
Kreisel
W
W
Heinrich
P C
PC
Gerok
W
W
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D009961:Orosomucoid / Q000096:biosynthesis*; D011233:Precipitin Tests; D051381:Rats; D011919:Rats, Inbred Strains; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis*
D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D009961:Orosomucoid; D000515:alpha 1-Antitrypsin; C045621:miglitol; D017485:1-Deoxynojirimycin; D000118:Acetylglucosaminidase; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D005944:Glucosamine