Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells

Simonetta Ferruzza, Maria Laura Scarino, Giuseppe Rotilio, Maria Rosa Ciriolo, Paolo Santaroni, Andrea Onetti Muda, Yula Sambuy

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number6 40-6
Publication statusPublished - Dec 1999


  • Copper-histidine
  • CuCl
  • F actin organization
  • Junctional proteins
  • Microvilli
  • PH
  • Recovery
  • Uptake

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)


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