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NC‐1059 increases paracellular permeability by altering Occludin, ZO‐1 and Actin Distribution
Author(s) -
Somasekharan Suma,
Quesnell Rebecca R,
Iwamoto Takeo,
Tomich John M,
Schultz Bruce D
Publication year - 2006
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.20.4.a352-c
Subject(s) - occludin , paracellular transport , tight junction , microbiology and biotechnology , chemistry , biophysics , immunolabeling , barrier function , actin , permeability (electromagnetism) , biology , biochemistry , membrane , immunology , immunohistochemistry
NC‐1059 is a synthetic channel‐forming peptide that provides for ion transport (Isc) across, and changes in barrier function of, a variety of epithelia. The goal of this study is to identify the mechanisms by which NC‐1059 increases epithelial paracellular permeability. NC‐1059 exposure causes a rapid decrease in transepithelial resistance (Rte) that is accompanied by an increase in dextran permeation rate which documents an effect on the paracellular pathway and suggests that tight junction proteins might be affected. Immunolabeling of occludin, ZO‐1 and actin and confocal microscopy reveal substantial redistribution or loss of these proteins upon exposure to 200 micromolar NC‐1059. The immunolabeling of the tight junction proteins done after 5, 15 and 30 minutes of NC‐1059 exposure reveal that the changes begin to occur in the first 15 minutes and the tight junctions are substantially altered within 30 minutes matching the pattern of the change in Rte observed with NC‐1059 exposure. The modulation of the epithelial barrier has therapeutic potential to increase the efficiency of drug delivery. (Supported by GM 074096‐01)