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 journalArticle

49 Citations (Scopus)

Abstract

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
Volume277
Issue number6 40-6
Publication statusPublished - Dec 1999

Fingerprint

Caco-2 Cells
Tight Junctions
Copper
Permeability
Actins
Zonula Occludens-1 Protein
Occludin
Mannitol
Cadherins
Microvilli
Electric Impedance
Actin Cytoskeleton
Histidine
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells. / Ferruzza, Simonetta; Scarino, Maria Laura; Rotilio, Giuseppe; Ciriolo, Maria Rosa; Santaroni, Paolo; Muda, Andrea Onetti; Sambuy, Yula.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 277, No. 6 40-6, 12.1999.

Research output: Contribution to journalArticle

Ferruzza, Simonetta ; Scarino, Maria Laura ; Rotilio, Giuseppe ; Ciriolo, Maria Rosa ; Santaroni, Paolo ; Muda, Andrea Onetti ; Sambuy, Yula. / Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1999 ; Vol. 277, No. 6 40-6.
@article{2ff7f0c8ce824e1abca4454820f853cf,
title = "Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells",
abstract = "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.",
keywords = "Copper-histidine, CuCl, F actin organization, Junctional proteins, Microvilli, PH, Recovery, Uptake",
author = "Simonetta Ferruzza and Scarino, {Maria Laura} and Giuseppe Rotilio and Ciriolo, {Maria Rosa} and Paolo Santaroni and Muda, {Andrea Onetti} and Yula Sambuy",
year = "1999",
month = "12",
language = "English",
volume = "277",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "6 40-6",

}

TY - JOUR

T1 - Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells

AU - Ferruzza, Simonetta

AU - Scarino, Maria Laura

AU - Rotilio, Giuseppe

AU - Ciriolo, Maria Rosa

AU - Santaroni, Paolo

AU - Muda, Andrea Onetti

AU - Sambuy, Yula

PY - 1999/12

Y1 - 1999/12

N2 - 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.

AB - 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.

KW - Copper-histidine

KW - CuCl

KW - F actin organization

KW - Junctional proteins

KW - Microvilli

KW - PH

KW - Recovery

KW - Uptake

UR - http://www.scopus.com/inward/record.url?scp=0033400532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033400532&partnerID=8YFLogxK

M3 - Article

C2 - 10600810

AN - SCOPUS:0033400532

VL - 277

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 6 40-6

ER -