ULTRASTRUCTURAL-CHANGES IN THE GOLGI-APPARATUS AND SECRETORY GRANULESOF HL-60 CELLS TREATED WITH THE IMINO SUGAR N-BUTYLDEOXYNOJIRIMYCIN

The imino sugar N-butyldeoxynojirimycin inhibits the N-linked oligosac charide processing enzymes alpha-glucosidases I and II, and the cerami de specific glucosyltransferase which catalyses the first step in gluc osphingolipid biosynthesis. We have studied the effects of this compou nd on the ultrastructure of HL-60 cells to identify novel activities o f this compound. Treatment of HL-60 cells with this imino sugar result s in several morphological changes within the cell, none of which resu lt in cytotoxicity. The plasma membrane stains heavily with potassium ferrocyanide within 30 min following addition of the compound to the m edium, and there is then a time dependent involvement of all other int racellular membranes. Secretory granules become enlarged and lose thei r dense core morphology and appear either empty and vacuolated or have low density contents. However, the most striking effect of NB-DNJ tre atment is on the Golgi apparatus. The Golgi exhibits a time-dependent change from typical Golgi morphology to a structure almost completely devoid of cisternae and consisting predominantly of vesicles. All the observed changes are fully reversible on withdrawal of the compound.