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 Fe-59 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.