Role of phospholipase Cγ-induced activation of protein kinase C∈ (PKC∈) and PKCβI in epidermal growth factor-mediated protection of tight junctions from acetaldehyde in Caco-2 cell monolayers

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Abstract

Epidermal growth factor (EGF) protects the intestinal epithelial tight junctions from acetaldehyde-induced insult. The role of phospholipase Cγ (PLCγ) and protein kinase C (PKC) isoforms in the mechanism of EGF-mediated protection of tight junction from acetaldehyde was evaluated in Caco-2 cell monolayers. EGF-mediated prevention of acetaldehyde-induced decrease in transepithelial electrical resistance and an increase in inulin permeability, and subcellular redistribution of occludin and ZO-1 was attenuated by reduced expression of PLCγ1 by short hairpin RNA. EGF induced a rapid activation of PLCγ1 and PLC-dependent membrane translocation of PKC∈ and PKCβI. Inhibition of PKC activity or selective interference of membrane translocation of PKC∈ and PKCβI by RACK interference peptides attenuated EGF-mediated prevention of acetaldehyde-induced increase in inulin permeability and redistribution of occludin and ZO-1. BAPTA-AM and thapsigargin blocked EGF-induced membrane translocation of PKCβI and attenuated EGF-mediated prevention of acetaldehyde-induced disruption of tight junctions. EGF-induced translocation of PKC∈ and PKCβI was associated with organization of F-actin near the perijunctional region. This study shows that PLCγ-mediated activation of PKC∈ and PKCβI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult.

Original languageEnglish (US)
Pages (from-to)3574-3583
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number6
DOIs
StatePublished - Feb 8 2008

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Caco-2 Cells
Acetaldehyde
Tight Junctions
Type C Phospholipases
Epidermal Growth Factor
Protein Kinase C
Monolayers
Chemical activation
Occludin
Inulin
Membranes
Permeability
Membrane Proteins
Acoustic impedance
Thapsigargin
Electric Impedance
Small Interfering RNA
Actins
Protein Isoforms
Calcium

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Role of phospholipase Cγ-induced activation of protein kinase C∈ (PKC∈) and PKCβI in epidermal growth factor-mediated protection of tight junctions from acetaldehyde in Caco-2 cell monolayers",
abstract = "Epidermal growth factor (EGF) protects the intestinal epithelial tight junctions from acetaldehyde-induced insult. The role of phospholipase Cγ (PLCγ) and protein kinase C (PKC) isoforms in the mechanism of EGF-mediated protection of tight junction from acetaldehyde was evaluated in Caco-2 cell monolayers. EGF-mediated prevention of acetaldehyde-induced decrease in transepithelial electrical resistance and an increase in inulin permeability, and subcellular redistribution of occludin and ZO-1 was attenuated by reduced expression of PLCγ1 by short hairpin RNA. EGF induced a rapid activation of PLCγ1 and PLC-dependent membrane translocation of PKC∈ and PKCβI. Inhibition of PKC activity or selective interference of membrane translocation of PKC∈ and PKCβI by RACK interference peptides attenuated EGF-mediated prevention of acetaldehyde-induced increase in inulin permeability and redistribution of occludin and ZO-1. BAPTA-AM and thapsigargin blocked EGF-induced membrane translocation of PKCβI and attenuated EGF-mediated prevention of acetaldehyde-induced disruption of tight junctions. EGF-induced translocation of PKC∈ and PKCβI was associated with organization of F-actin near the perijunctional region. This study shows that PLCγ-mediated activation of PKC∈ and PKCβI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult.",
author = "Takuya Suzuki and Ankur Seth and Radhakrishna Rao",
year = "2008",
month = "2",
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doi = "10.1074/jbc.M709141200",
language = "English (US)",
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publisher = "American Society for Biochemistry and Molecular Biology Inc.",
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T1 - Role of phospholipase Cγ-induced activation of protein kinase C∈ (PKC∈) and PKCβI in epidermal growth factor-mediated protection of tight junctions from acetaldehyde in Caco-2 cell monolayers

AU - Suzuki, Takuya

AU - Seth, Ankur

AU - Rao, Radhakrishna

PY - 2008/2/8

Y1 - 2008/2/8

N2 - Epidermal growth factor (EGF) protects the intestinal epithelial tight junctions from acetaldehyde-induced insult. The role of phospholipase Cγ (PLCγ) and protein kinase C (PKC) isoforms in the mechanism of EGF-mediated protection of tight junction from acetaldehyde was evaluated in Caco-2 cell monolayers. EGF-mediated prevention of acetaldehyde-induced decrease in transepithelial electrical resistance and an increase in inulin permeability, and subcellular redistribution of occludin and ZO-1 was attenuated by reduced expression of PLCγ1 by short hairpin RNA. EGF induced a rapid activation of PLCγ1 and PLC-dependent membrane translocation of PKC∈ and PKCβI. Inhibition of PKC activity or selective interference of membrane translocation of PKC∈ and PKCβI by RACK interference peptides attenuated EGF-mediated prevention of acetaldehyde-induced increase in inulin permeability and redistribution of occludin and ZO-1. BAPTA-AM and thapsigargin blocked EGF-induced membrane translocation of PKCβI and attenuated EGF-mediated prevention of acetaldehyde-induced disruption of tight junctions. EGF-induced translocation of PKC∈ and PKCβI was associated with organization of F-actin near the perijunctional region. This study shows that PLCγ-mediated activation of PKC∈ and PKCβI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult.

AB - Epidermal growth factor (EGF) protects the intestinal epithelial tight junctions from acetaldehyde-induced insult. The role of phospholipase Cγ (PLCγ) and protein kinase C (PKC) isoforms in the mechanism of EGF-mediated protection of tight junction from acetaldehyde was evaluated in Caco-2 cell monolayers. EGF-mediated prevention of acetaldehyde-induced decrease in transepithelial electrical resistance and an increase in inulin permeability, and subcellular redistribution of occludin and ZO-1 was attenuated by reduced expression of PLCγ1 by short hairpin RNA. EGF induced a rapid activation of PLCγ1 and PLC-dependent membrane translocation of PKC∈ and PKCβI. Inhibition of PKC activity or selective interference of membrane translocation of PKC∈ and PKCβI by RACK interference peptides attenuated EGF-mediated prevention of acetaldehyde-induced increase in inulin permeability and redistribution of occludin and ZO-1. BAPTA-AM and thapsigargin blocked EGF-induced membrane translocation of PKCβI and attenuated EGF-mediated prevention of acetaldehyde-induced disruption of tight junctions. EGF-induced translocation of PKC∈ and PKCβI was associated with organization of F-actin near the perijunctional region. This study shows that PLCγ-mediated activation of PKC∈ and PKCβI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult.

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