Nystatin affects zinc uptake in human fibroblasts.
The mechanism(s) by which zinc is transported into cells has not been identified. Since zinc uptake is inhibited by reducing the temperature, zinc uptake may depend on the movement of plasma membrane micoenvironments, such as endocytosis or potocytosis. We investigated the potential role of potocytosis in cellular zinc uptake by incubating normal and acrodermatitis enteropathica fibroblasts with nystatin, a sterol-binding drug previously shown to inhibit potocytosis. Zinc uptake was determined during initial rates of uptake (10 min) following incubation of the fibroblasts in 50 micrograms nystatin/mL or 0.1% dimethylsulfoxide for 10 min at 37 degrees C. The cells were then incubated with 1 to 30 microM 65zinc. Michaelis-Menten kinetics were observed for zinc uptake. Nystatin inhibited zinc uptake in both the normal and AE fibroblasts. Reduced cellular uptake of zinc was associated with its internalization, not its external binding. In normal fibroblasts, nystatin significantly reduced the K(m) 56% and the Vmax 69%. In the AE fibroblasts, nystatin treatment significantly reduced the Vmax 59%, but did not significantly affect the K(m). The AE mutation alone affected the Vmax for cellular zinc uptake. The control AE fibroblasts exhibited a 40% reduction in Vmax compared to control normal fibroblasts. We conclude that nystatin exerts its effect on zinc uptake by reducing the velocity at which zinc traverses the cell membrane, possibly through potocytosis. Furthermore, the AE mutation also affects zinc transport by reducing zinc transport.
Grider
A
A
Division of Nutritional Sciences, University of Texas, Austin 78712, USA.
Vazquez
F
F
D019325:3-O-Methylglucose / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D009761:Nystatin / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism*
D007476:Ionophores; D009761:Nystatin; D019325:3-O-Methylglucose; D015032:Zinc; D004121:Dimethyl Sulfoxide