Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions.

Parimal Sheth, Shyamali Basuroy, Chunyang Li, Anjaparavanda P. Naren, Radhakrishna Rao

Research output: Contribution to journalArticle

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Abstract

A recent study (Nusrat, A., Chen, J. A., Foley, C. S., Liang, T. W., Tom, J., Cromwell, M., Quan, C., and Mrsny, R. J. (2000) J. Biol. Chem. 275, 29816-29822) suggested that phosphatidylinositol 3-kinase (PI 3-kinase) may interact with occludin; however, there exists no evidence of direct interaction of PI 3-kinase with the tight junctions. Activation of PI 3-kinase by oxidative stress and its role in disruption of tight junctions was examined in Caco-2 cell monolayer. The oxidative stress-induced decrease in electrical resistance, increase in inulin permeability, and redistribution of occludin and ZO-1 were reduced by a PI 3-kinase inhibitor, LY294002. Oxidative stress-induced tyrosine phosphorylation and dissociation from the actin cytoskeleton of occludin and ZO-1 were reduced by LY294002. The regulatory subunit of PI 3-kinase, p85, and the PI 3-kinase activity were co-immunoprecipitated with occludin, which were rapidly increased by oxidative stress. Oxidative stress resulted in increased translocation of p85 from the intracellular compartment into the intercellular junctions. Pair-wise glutathione S-transferase pull-down assay showed that glutathione S-transferase-occludin (C-terminal tail) binds to recombinant p85. This study shows that oxidative stress increases the association of PI 3-kinase with the occludin, and that PI 3-kinase activity is involved in oxidative stress-induced disruption of tight junction.

Original languageEnglish (US)
Pages (from-to)49239-49245
Number of pages7
JournalThe Journal of biological chemistry
Volume278
Issue number49
DOIs
StatePublished - Jan 1 2003

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Phosphatidylinositol 3-Kinase
Oxidative stress
Tight Junctions
Occludin
Oxidative Stress
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Glutathione Transferase
Phosphorylation
Acoustic impedance
Intercellular Junctions
Caco-2 Cells
Inulin
Electric Impedance
Actin Cytoskeleton
Tyrosine
Actins
Monolayers
Permeability
Assays
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions. / Sheth, Parimal; Basuroy, Shyamali; Li, Chunyang; Naren, Anjaparavanda P.; Rao, Radhakrishna.

In: The Journal of biological chemistry, Vol. 278, No. 49, 01.01.2003, p. 49239-49245.

Research output: Contribution to journalArticle

Sheth, Parimal ; Basuroy, Shyamali ; Li, Chunyang ; Naren, Anjaparavanda P. ; Rao, Radhakrishna. / Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions. In: The Journal of biological chemistry. 2003 ; Vol. 278, No. 49. pp. 49239-49245.
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