Effects of the alpha-mannosidase inhibitors, 1,4-dideoxy-1,4-imino-D-mannitol and swainsonine, on glycoprotein catabolism in cultured macrophages.
Thioglycollate-stimulated murine peritoneal macrophages were cultured for eight days in the presence of swainsonine, or 1,4-dideoxy-1,4-imino-D-mannitol (DIM), or both of these competitive alpha-mannosidase inhibitors together. Analysis of accumulated high-mannose oligosaccharides by reversed phase HPLC after perbenzoylation revealed that DIM- and DIM-plus swainsonine-treated macrophages contained larger amounts of Man7GlcNAc, Man8GlcNAc and Man9GlcNAc, while swainsonine-treated macrophages contained relatively more Man3GlcNAc and Man5GlcNAc. These results are consistent with the known inhibitory effects of DIM and swainsonine on Golgi mannosidases I and II, respectively, and on lysosomal alpha-mannosidase. Depletion of stored oligosaccharides to control values was complete within seven days of terminating swainsonine treatment.
Daniel
P F
PF
Department of Biochemistry, E.K. Shriver Center, Waltham, MA 02254.
Newburg
D S
DS
O'Neil
N E
NE
Smith
P W
PW
Fleet
G W
GW
D017485:1-Deoxynojirimycin; D000818:Animals; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000652:urine; D017026:Swainsonine / Q000494:pharmacology*; D043323:alpha-Mannosidase; D008363:alpha-Mannosidosis / Q000652:urine
D006023:Glycoproteins; D009844:Oligosaccharides; D017485:1-Deoxynojirimycin; D008361:Mannosidases; D043323:alpha-Mannosidase; D005944:Glucosamine; D017026:Swainsonine