Inhibition of myoblast fusion by bromoconduritol.
It has recently been reported that the glucosidase I inhibitor, N-methyl-1-deoxynojirimycin (MDJN), inhibits myoblast fusion whereas the mannosidase inhibitor, 1-deoxymannojirimycin (ManDJN), has no effect on fusion. We now report that bromoconduritol, which is an active-site-directed covalent inhibitor of glucosidase II, also inhibits fusion at concentrations that have no effect on the plating efficiency or growth of rat L6 myoblasts. Significant inhibition of fusion was obtained at concentrations as low as 50 micrograms of bromoconduritol/mL, whereas inhibition of cell growth did not occur until concentrations of 250 micrograms/mL were reached. Rat L6 myoblasts were grown in the presence and absence of processing inhibitors and were surface labelled with 125I. Analysis of the iodinated proteins by two-dimensional gel electrophoresis demonstrated that a number of high-molecular-weight proteins (greater than 90,000) detected at the surface of control cells were absent from the surface of cells treated with MDJN or bromoconduritol. It is suggested that MDJN and bromoconduritol prevent the translocation of these proteins to the cell surface. The high-molecular-weight proteins detected at the surface of control cells were also detectable in ManDJN-treated cells, indicating that inhibition of N-linked complex oligosaccharide formation does not affect the translocation of these proteins to the myoblast cell surface.
Trudel
G C
GC
Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Que., Canada.
Herscovics
A
A
Holland
P C
PC
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002384:Catalysis; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D053138:Cyclohexenes; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007784:Lactoperoxidase / Q000494:pharmacology; D008565:Membrane Proteins / Q000032:analysis; D008970:Molecular Weight; D009132:Muscles / Q000166:cytology / Q000187:drug effects*; D051381:Rats
D000900:Anti-Bacterial Agents; D053138:Cyclohexenes; D008565:Membrane Proteins; D017485:1-Deoxynojirimycin; C036388:6-bromoconduritol; D007294:Inositol; D007784:Lactoperoxidase; D005959:Glucosidases; D005944:Glucosamine; C033424:N-methyldeoxynojirimycin