The Role of Protein Kinase C Isoforms in Modulating Injury and Repair of the Intestinal Barrier

Farhadi, Ashkan; Keshavarzian, Ali; Ranjbaran, Ziba; Fields, Jeremy Z.; Banan, Ali

doi:10.1124/jpet.105.085449

Cited by 81 publications

(58 citation statements)

References 52 publications

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“…Evidence indicates that PKC activity is involved in the EGF-mediated protection of TJ from oxidative stress (7). To determine the mechanism involved in the probiotic-mediated protection of TJ from H 2 O 2 , we investigated the role of PKC activity in probiotic-mediated protection of TJ.…”

Section: Resultsmentioning

confidence: 99%

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Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism

Seth

Yan

Polk

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

330

256

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Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and beta-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKCbetaI and PKCepsilon. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism.

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Section: Resultsmentioning

confidence: 99%

“…Evidence suggests that PKC activity may be involved in EGF-mediated protection of the intestinal epithelial barrier function from oxidative stress (7). Therefore, we evaluated the role of PKC activity in the p40-and p75-mediated protection of TJ from H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism

Seth

Yan

Polk

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

330

256

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show abstract

“…Several PKC isoforms have roles in epithelial barrier function (16), so we tested a panel of PKC inhibitors and activators in our Ussing chamber experiments to determine their possible involvement (Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

Serine proteases decrease intestinal epithelial ion permeability by activation of protein kinase Cζ

Swystun

Renaux²,

Wen³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Epithelial permeability to ions and larger molecules in the gut is essential for fluid balance, and its dysregulation contributes to intestinal pathology. We investigated the effect of digestive serine proteases on epithelial paracellular permeability. Trypsin, chymotrypsin, and elastase elicited sustained increases in transepithelial resistance (R(TE)) in polarized monolayers of three intestinal epithelial cell lines. This effect was reflected by decreases in paracellular conductances of Na+ and Cl- and a concomitant decrease in permeability to 3,000 molecular weight dextran. The enzyme activities of the proteases were required, yet activators of known protease-activated receptors (PARs) did not reproduce the effect of these proteases on R(TE). PKCzeta isoform-specific inhibitor significantly reduced the trypsin-induced increase in R(TE) whereas PKCzeta activity was increased in cells treated with trypsin and chymotrypsin compared with control cells; this activity was reduced to control levels in the presence of PKCzeta-specific inhibitor. Ca2+ chelators and pharmacological inhibitors of cell signaling support the role for PKCzeta in the protease-induced effect. Finally, we showed that treatment with the serine proteases increased occludin immunostaining and zonula occludin-1 coimmunoprecipitation with occludin in the detergent-insoluble fraction of cell lysates, and these increases were ablated by pretreatment with PKCzeta-specific inhibitor. This finding indicates increased insertion of occludin into the cell junctional complex. These data demonstrate a role for serine proteases in the facilitation of epithelial barrier function through a mechanism that is independent of PARs and is mediated by activation of PKCzeta.

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“…8), indicating that at least in selected cell types, OspE-independent factors, perhaps including vacuole escape (34), also contribute to activation of PKC by Shigella. Isoforms of PKC control intracellular pathways that regulate cell morphology and barrier function (35), and PKC activity is correlated with increased cell spreading and adherence (36), suggesting functional roles for PKC activation in Shigella infection. , not significant; a.u., arbitrary units.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Bacterial Effector-Postsynaptic Density 95/Disc Large/Zonula Occludens-1 (PDZ) Domain Interactions Demonstrates Shigella OspE Protein Promotes Protein Kinase C Activation via PDLIM Proteins

Allen

Russo

et al. 2014

Journal of Biological Chemistry

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Background: PDZ domains provide specificity in protein-protein interactions in eukaryotic systems. Results: Shigella OspE, which is delivered into human cells during infection, binds PDLIM7 via a PDZ interaction and contributes to activation of PKC. Conclusion: During infection, OspE contributes to activation of PKC through PDZ-mediated binding to PDLIM7. Significance: PDZ interactions likely contribute to pathogenesis of several bacterial pathogens.

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The Role of Protein Kinase C Isoforms in Modulating Injury and Repair of the Intestinal Barrier

Cited by 81 publications

References 52 publications

Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism

Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism

Serine proteases decrease intestinal epithelial ion permeability by activation of protein kinase Cζ

Systematic Analysis of Bacterial Effector-Postsynaptic Density 95/Disc Large/Zonula Occludens-1 (PDZ) Domain Interactions Demonstrates Shigella OspE Protein Promotes Protein Kinase C Activation via PDLIM Proteins

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