The effect of the acrodermatitis enteropathica mutation on zinc uptake in human fibroblasts

Abstract

The acrodermatitis enteropathica (AE) mutation affects intestinal zinc absorption. Our goal was to determine whether the AE mutation affects zinc uptake in human fibroblasts. Zinc uptake was determined during initial rates of uptake (10 min) following incubation in HEPES/saline buffer. Zinc uptake (from 0.25 to 1 μM) into normal fibroblasts was significantly greater than into the AE fibroblasts (p<0.05). In order to identify factors that may alter cellular zinc uptake and be affected by the AE mutation, zinc uptake in the presence of albumin or bicarbonate was measured. Albumin restricted zinc uptake in both normal and AE fibroblasts, whereas bicarbonate stimulated zinc uptake in the normal fibroblasts. The effect of bicarbonate on zinc uptake in the AE fibroblasts was significantly reduced in both the Pronase-sensitive and Pronase-resistant compartments. Following loading of the fibroblasts with 1 μM zinc for 60 min, zinc efflux and retention were measured. The AE mutation did not affect zinc retention compared to normal fibroblasts. We conclude that the AE mutation affects both zinc binding to the cell surface and its translocation across the plasma membrane into the cell, possibly mediated through a defective anionic exchange mechanism.