Modulation of cell‐surface transferrin receptor by the imino sugar N‐butyldeoxynojirimycin

Abstract

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.