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NC‐1059, a synthetic peptide, induces a reversible reorganization of the junctional proteins
Author(s) -
Somasekharan Suma,
Tomich John M,
Schultz Bruce D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1429-c
Subject(s) - paracellular transport , chemistry , occludin , tight junction , peptide , monolayer , biophysics , permeation , permeability (electromagnetism) , microbiology and biotechnology , membrane , biochemistry , biology
The goal of this study is to identify the mechanism(s) by which NC‐1059, a synthetic channel forming peptide, increases epithelial paracellular permeability. Apical exposure to NC‐1059 concentration‐dependently increases short circuit current ( I sc ) and decreases transepithelial electrical resistance ( R te ) across a variety of epithelia. Concomitantly, NC‐1059 enhances the permeation rate of large molecular weight dextrans across monolayers, which documents a peptide induced opening of the paracellular route. Previous studies from this laboratory showed that the NC‐1059‐induced (60 μM) change in R te returns to pretreatment levels within 48 hours. In this study MDCK monolayers exposed to 100 μM NC‐1059 for 60 minutes showed a partial recovery in R te at 24 hours and returned to pretreatment values at 48 hours. Partial recovery in R te is observed at 24 and 48 hours when greater NC‐1059 concentrations are employed. MDCK monolayers exposed to NC‐1059 reveal a substantial reorganization or loss of actin and junctional protein (occludin, ZO‐1, E‐cadherin and β‐catenin) labeling within one hour with ongoing recovery of protein distribution observed at 24 and 48 hour post exposure. The modulation of the epithelial tight junctions in a reversible manner has therapeutic potential to increase the efficiency of drug delivery across barrier membranes. (Supported by GM 074096 to JMT and P20 RRO17686 )