Modulation of cell-surface transferrin receptor by the imino sugar N-butyldeoxynojirimycin.
The imino sugar, N-butyldeoxynojirimycin, is an inhibitor of the glycoprotein-processing enzyme glucosidase I and exhibits anti-(human immunodeficiency virus) activity in vitro. We have investigated the effect(s) of this compound on cell-surface glycoproteins by flow cytometry. We observed selective modulation of the transferrin receptor in response to treatment with 0.5 mM N-butyldeoxynojirimycin resulting in reduced cell-surface transferrin-receptor expression. The receptor modulation was dose dependent, resulted in reduced 59Fe uptake by treated cells and was fully reversible within 24 h of culture in the absence of the compound. Pulse/chase analysis in conjunction with endoglycosidase-H digestion demonstrated that transferrin-receptor glycosylation was altered following N-butyldeoxynojirimycin treatment, which is compatible with glucosidase inhibition. In addition, modulation of transferrin receptor in response to N-butyldeoxynojirimycin was not confined to a single cell line, but was also observed with certain human lymphoid and myeloid cell lines. Mechanism(s) of action of the imino sugar resulting in reduced cell-surface transferrin-receptor expression are discussed.
Platt
F M
FM
Department of Biochemistry, University of Oxford, England.
Karlsson
G B
GB
Jacob
G S
GS
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D006678:HIV / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D000998:Antiviral Agents; D011990:Receptors, Transferrin; D014168:Transferrin; D017485:1-Deoxynojirimycin; C059896:miglustat; D006026:Glycoside Hydrolases; D005944:Glucosamine