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Lookup NU author(s): Dr Simon BamforthORCiD
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Tight junctions (TJs), the most apical of the intercellular junctions, prevent the passage of ions and molecules through the paracellular pathway. Intracellular signalling molecules are likely to be involved in the regulation of TJ integrity. In order to specifically investigate the role of protein kinase A (PKA) in the maintenance of epithelial TJ integrity, calcium-switch experiments were performed, in which calcium was removed from EpH4 and MDCK culture medium, in the absence or presence of the PKA inhibitors H-89 or HA-1004. Removal of calcium from the culture media of the epithelial cells resulted in disruption of the TJs, characterised by a loss of membrane association of the TJ-associated proteins occludin, ZO-1 and ZO-2, by a loss of TJ strands, by a marked decrease in the transepithelial electrical resistance and by a dramatic increase in the transepithelial permeability to tracers. The association of occludin, ZO-1 and ZO-2 with the actin cytoskeleton is not affected. In contrast, when the removal of calcium was performed in the presence of either the PKA inhibitor H-89 or HA-1004, all barrier characteristics were preserved. Our data indicate that following the removal of calcium from the culture medium of epithelial cells in vitro, PKA is activated and subsequently is involved in the disruption of TJs.
Author(s): Bamforth SD; Klingler C; Kniesel U; Wolburg H; Engelhardt B; Risau W
Publication type: Article
Publication status: Published
Journal: Histochemistry and Cell Biology
Year: 2000
Volume: 113
Issue: 5
Pages: 349-361
ISSN (print): 0948-6143
ISSN (electronic): 1432-119X
Publisher: Springer
URL: http://www.springerlink.com/content/8awuc977fd0829vm/fulltext.pdf
DOI: 10.1007/s004180000143
Notes: 0948-6143 (Print) Journal Article
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