The effects of copper on tight-junction permeability were investigated in human intestinal Caco-2 cells, monitoring transepithelial electrical resistance and transepithelial passage of mannitol. Apical treatment of Caco- 2 cells with 10-100 μM CuCl2 (up to 3 h) produced a time- and concentration-dependent increase in tight-junction permeability, reversible after 24 h in complete medium in the absence of added copper. These effects were not observed in cells treated with copper complexed to = L-histidine [Cu(His)2]. The copper-induced increase in tight-junction permeability was affected by the pH of the apical medium, as was the apical uptake of 64CuCl2, both exhibiting a maximum at pH 6.0. Treatment with CuCl2 produced a concentration-dependent reduction in the staining of F actin but not of the junctional proteins zonula occludens-1, occludin, and E-cadherin and produced ultrastructural alterations to microvilli and tight junctions that were not observed after treatment with up to 200 μM Cu(His)2 for 3 h. Overall, these data point to an intracellular effect of copper on tight junctions, mediated by perturbations of the F actin cytoskeleton.
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Issue number||6 40-6|
|Publication status||Published - Dec 1999|
- F actin organization
- Junctional proteins
ASJC Scopus subject areas
- Physiology (medical)