Oxidant-induced disruption of intestinal epithelial barrier function

Role of protein tyrosine phosphorylation

Radhakrishna Rao, R. D. Baker, S. S. Baker, A. Gupta, M. Holycross

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

The effect of hydrogen peroxide (H2O2) on intestinal epithelial barrier function was examined in Caco-2 and T84 cell monolayers. H2O2 reduced transepithelial electrical resistance (TER) of Caco-2 and T84 cell monolayers. This decrease in TEE was associated with a decrease in dilution potential and an increase in [3H]mannitol permeability, suggesting an H2O2-induced disruption of the paracellular junctional complexes, H2O2 administration also induced tyrosine phosphorylation of several proteins (at the molecular mass ranges of 50-90, 100-130, and 150-180 kDa) in Caco-2 cell monolayers. Phenylarsine oxide and sodium orthovanadate, inhibitors of protein tyrosine phosphatase, decreased TER and increased mannitol permeability and protein tyrosine phosphorylation (PTP). A low concentration of sodium orthovanadate also potentiated the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. Pretreatment with genistein (30-300 μM) and tyrphostin (100 μM) inhibited the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. These studies show that H2O2 increases the epithelial permeability by disrupting paracellular junctional complexes, most likely by a PTP-dependent mechanism.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume273
Issue number4 36-4
StatePublished - Nov 15 1997
Externally publishedYes

Fingerprint

Oxidants
Tyrosine
Mannitol
Permeability
Electric Impedance
Phosphorylation
Caco-2 Cells
Vanadates
Proteins
Sodium
Tyrphostins
Protein Tyrosine Phosphatases
Genistein
Hydrogen Peroxide

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Oxidant-induced disruption of intestinal epithelial barrier function : Role of protein tyrosine phosphorylation. / Rao, Radhakrishna; Baker, R. D.; Baker, S. S.; Gupta, A.; Holycross, M.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 273, No. 4 36-4, 15.11.1997.

Research output: Contribution to journalArticle

@article{b23e93a87f0448418240154a7df2aa40,
title = "Oxidant-induced disruption of intestinal epithelial barrier function: Role of protein tyrosine phosphorylation",
abstract = "The effect of hydrogen peroxide (H2O2) on intestinal epithelial barrier function was examined in Caco-2 and T84 cell monolayers. H2O2 reduced transepithelial electrical resistance (TER) of Caco-2 and T84 cell monolayers. This decrease in TEE was associated with a decrease in dilution potential and an increase in [3H]mannitol permeability, suggesting an H2O2-induced disruption of the paracellular junctional complexes, H2O2 administration also induced tyrosine phosphorylation of several proteins (at the molecular mass ranges of 50-90, 100-130, and 150-180 kDa) in Caco-2 cell monolayers. Phenylarsine oxide and sodium orthovanadate, inhibitors of protein tyrosine phosphatase, decreased TER and increased mannitol permeability and protein tyrosine phosphorylation (PTP). A low concentration of sodium orthovanadate also potentiated the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. Pretreatment with genistein (30-300 μM) and tyrphostin (100 μM) inhibited the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. These studies show that H2O2 increases the epithelial permeability by disrupting paracellular junctional complexes, most likely by a PTP-dependent mechanism.",
author = "Radhakrishna Rao and Baker, {R. D.} and Baker, {S. S.} and A. Gupta and M. Holycross",
year = "1997",
month = "11",
day = "15",
language = "English (US)",
volume = "273",
journal = "American Journal of Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4 36-4",

}

TY - JOUR

T1 - Oxidant-induced disruption of intestinal epithelial barrier function

T2 - Role of protein tyrosine phosphorylation

AU - Rao, Radhakrishna

AU - Baker, R. D.

AU - Baker, S. S.

AU - Gupta, A.

AU - Holycross, M.

PY - 1997/11/15

Y1 - 1997/11/15

N2 - The effect of hydrogen peroxide (H2O2) on intestinal epithelial barrier function was examined in Caco-2 and T84 cell monolayers. H2O2 reduced transepithelial electrical resistance (TER) of Caco-2 and T84 cell monolayers. This decrease in TEE was associated with a decrease in dilution potential and an increase in [3H]mannitol permeability, suggesting an H2O2-induced disruption of the paracellular junctional complexes, H2O2 administration also induced tyrosine phosphorylation of several proteins (at the molecular mass ranges of 50-90, 100-130, and 150-180 kDa) in Caco-2 cell monolayers. Phenylarsine oxide and sodium orthovanadate, inhibitors of protein tyrosine phosphatase, decreased TER and increased mannitol permeability and protein tyrosine phosphorylation (PTP). A low concentration of sodium orthovanadate also potentiated the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. Pretreatment with genistein (30-300 μM) and tyrphostin (100 μM) inhibited the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. These studies show that H2O2 increases the epithelial permeability by disrupting paracellular junctional complexes, most likely by a PTP-dependent mechanism.

AB - The effect of hydrogen peroxide (H2O2) on intestinal epithelial barrier function was examined in Caco-2 and T84 cell monolayers. H2O2 reduced transepithelial electrical resistance (TER) of Caco-2 and T84 cell monolayers. This decrease in TEE was associated with a decrease in dilution potential and an increase in [3H]mannitol permeability, suggesting an H2O2-induced disruption of the paracellular junctional complexes, H2O2 administration also induced tyrosine phosphorylation of several proteins (at the molecular mass ranges of 50-90, 100-130, and 150-180 kDa) in Caco-2 cell monolayers. Phenylarsine oxide and sodium orthovanadate, inhibitors of protein tyrosine phosphatase, decreased TER and increased mannitol permeability and protein tyrosine phosphorylation (PTP). A low concentration of sodium orthovanadate also potentiated the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. Pretreatment with genistein (30-300 μM) and tyrphostin (100 μM) inhibited the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. These studies show that H2O2 increases the epithelial permeability by disrupting paracellular junctional complexes, most likely by a PTP-dependent mechanism.

UR - http://www.scopus.com/inward/record.url?scp=0030869798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030869798&partnerID=8YFLogxK

M3 - Article

VL - 273

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1931-857X

IS - 4 36-4

ER -