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Involvement of protein kinase C in chitosan glutamate-mediated tight junction disruption

Paper ID Volume ID Publish Year Pages File Format Full-Text
12276 786 2005 8 PDF Available
Title
Involvement of protein kinase C in chitosan glutamate-mediated tight junction disruption
Abstract

Chitosan has been successfully used as an excipient for trans-epithelial drug delivery systems. It is known to transiently open intercellular tight junctions thus increasing the permeability of an epithelium. In order to investigate the possible role of protein kinases in trans-epithelial delivery, changes in trans-epithelial electrical resistance (‘TEER’) of epithelial (Caco-2) cell monolayers were assessed in response to chitosan glutamate treatment, in the presence and absence of specific protein kinase inhibitors. Changes in subcellular localisation of the tight junction protein ZO-1 observed by immunofluorescence and western blotting of cellular fractions were also assessed. Inhibition of protein kinase C (PKC), but not mitogen activated protein kinase (MAPK) was found to prevent the chitosan-mediated decrease in TEER, and changes in localisation of ZO-1. In order to determine which PKC isozymes were responsible for the chitosan-mediated tight junction disruption, the activation of the PKC isozymes α, β and δ was investigated. A chitosan-mediated translocation of PKC α but not PKC β or δ from the cytosol to the membrane fraction, indicative of PKC α activation was observed. Thus, treatment of Caco-2 cells with chitosan may result in the activation of PKC-dependent signal transduction pathways which affect tight junction integrity.

Keywords
Chitosan; Cell adhesion; Cell signalling; Drug delivery; Epithelium
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Involvement of protein kinase C in chitosan glutamate-mediated tight junction disruption
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 26, Issue 16, June 2005, Pages 3269–3276
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us