Hepatocyte specific long lasting inhibition of protein N-glycosylation by D-galactosamine.
The effect of D-galactosamine on protein N-glycosylation was studied in rat hepatocyte primary cultures for alpha 1-antitrypsin (three complex type oligosaccharide chains) and alpha 1-acid glycoprotein (six complex type oligosaccharide chains). D-Galactosamine at a concentration of 4 mM inhibited partially de novo N-glycosylation leading to the formation of alpha 1-antitrypsin lacking one to two and of alpha 1-acid glycoprotein lacking one to five of its carbohydrate side chains. In addition D-galactosamine interfered with oligosaccharide processing, leading to the formation of some carbohydrate side chains remaining in an endoglucosaminidase H sensitive, i.e., not completely processed, form. D-Galactosamine impaired the secretion of alpha 1-antitrypsin and of alpha 1-acid glycoprotein but did not inhibit the secretion of the unglycosylated albumin. The inhibitory effect of D-galactosamine on de novo glycosylation as well as on oligosaccharide processing lasted for at least 24 h after it had been removed from the cells. D-Galactosamine impaired the glycosylation of alpha 1-antitrypsin only in hepatocytes, but not in human monocytes. Furthermore, D-galactosamine did not impair the N- and O-glycosylation of interleukin-6 in human monocytes and in MRC 5 fibroblasts. The results indicate that the effect of D-galactosamine on protein glycosylation is restricted to D-galactosamine metabolizing hepatocytes and is not exerted by the drug itself but by its metabolites.
Gross
V
V
Medizinische Universitätsklinik Albert Ludwigs Universität, Freiburg, F.R.G.
Ludolph
D
D
Vom Berg
D
D
Kreisel
W
W
Andus
T
T
Katz
N
N
Giffhorn-Katz
S
S
Heinrich
P C
PC
Gerok
W
W
D000118:Acetylglucosaminidase; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D005688:Galactosamine / Q000494:pharmacology*; D005944:Glucosamine / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009961:Orosomucoid / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000235:genetics
D015850:Interleukin-6; D009961:Orosomucoid; D000515:alpha 1-Antitrypsin; D005688:Galactosamine; D000118:Acetylglucosaminidase; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D005944:Glucosamine