Role of Phospholipase Cγ-induced Activation of Protein Kinase Cϵ (PKCϵ) and PKCβI in Epidermal Growth Factor-mediated Protection of Tight Junctions from Acetaldehyde in Caco-2 Cell Monolayers
Copyright policy )Role of Phospholipase Cγ-induced Activation of Protein Kinase Cϵ (PKCϵ) and PKCβI in Epidermal Growth Factor-mediated Protection of Tight Junctions from Acetaldehyde in Caco-2 Cell Monolayers
Epidermal growth factor (EGF) protects the intestinal epithelial tight junctions from acetaldehyde-induced insult. The role of phospholipase Cgamma (PLCgamma) 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 PLCgamma1 by short hairpin RNA. EGF induced a rapid activation of PLCgamma1 and PLC-dependent membrane translocation of PKCepsilon and PKCbetaI. Inhibition of PKC activity or selective interference of membrane translocation of PKCepsilon and PKCbetaI 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 PKCbetaI and attenuated EGF-mediated prevention of acetaldehyde-induced disruption of tight junctions. EGF-induced translocation of PKCepsilon and PKCbetaI was associated with organization of F-actin near the perijunctional region. This study shows that PLCgamma-mediated activation of PKCepsilon and PKCbetaI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult.
- University of Tennessee Health Science Center United States
- University of Tennessee System United States
Epidermal Growth Factor, Phospholipase C gamma, Cell Membrane, Membrane Proteins, Acetaldehyde, Protein Kinase C-epsilon, Models, Biological, Tight Junctions, Gene Expression Regulation, Neoplastic, Protein Transport, Occludin, Protein Kinase C beta, Humans, Caco-2 Cells, Peptides, Egtazic Acid, Protein Kinase C
Epidermal Growth Factor, Phospholipase C gamma, Cell Membrane, Membrane Proteins, Acetaldehyde, Protein Kinase C-epsilon, Models, Biological, Tight Junctions, Gene Expression Regulation, Neoplastic, Protein Transport, Occludin, Protein Kinase C beta, Humans, Caco-2 Cells, Peptides, Egtazic Acid, Protein Kinase C
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