The Na+/H+ exchange inhibitor HOE642 prevents stress-induced epithelial barrier dysfunction

Recently, evidence has been obtained that the Na+/H+ exchange (NHE) inhibitor HOE642 may stabilize endothelial and epithelial barrier function in vivo. However, the underlying mechanisms are not known. Therefore, we studied the influence of HOE642 on the barrier function of the epithelial cell line CaCo2. The phorbolester phorbol 12-myristate 13-acetate (PMA) was used to induce hyperpermeability of the epithelial layer which was indirectly determined by measuring the transepithelial electrical resistance (TER). Confocal laser scan microscopy (LSM) served to analyze the intracellular localization of adherens and tight junction molecules. In five independent experiments we found that HOE642 increased TER in non-treated CaCo2 cells (control: 350 +/- 28 Omega/cm2; HOE642: 444 +/- 53 Omega/cm2) and prevented PMA-induced barrier dysfunction (PMA: 33 +/- 12 Omega/cm2; PMA plus HOE642: 496 +/- 47 Omega/cm2). LSM showed that HOE642 prevented the PMA-induced disassociation of the zonula adherens molecule beta-catenin from the cell membrane and the decreased expression of the zonula occludens molecule ZO-1. From our data we conclude that HOE642 may prevent stress-induced epithelial dysfunction by stabilization of cell membrane-associated junction molecules.

Medienart:

Artikel

Erscheinungsjahr:

2004

Erschienen:

2004

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

International journal of molecular medicine - 14(2004), 2 vom: 21. Aug., Seite 175-8

Sprache:

Englisch

Beteiligte Personen:

Nowak, Peter [VerfasserIn]
Blaheta, Roman [VerfasserIn]
Schuller, Alina [VerfasserIn]
Cinatl, Jindrich [VerfasserIn]
Wimmer-Greinecker, Gerhard [VerfasserIn]
Moritz, Anton [VerfasserIn]
Scholz, Martin [VerfasserIn]

Themen:

7E3392891K
Anti-Arrhythmia Agents
Beta Catenin
CTNNB1 protein, human
Carcinogens
Cariporide
Cytoskeletal Proteins
Guanidines
Journal Article
NI40JAQ945
Sodium-Hydrogen Exchangers
Sulfones
Tetradecanoylphorbol Acetate
Trans-Activators

Anmerkungen:

Date Completed 04.03.2005

Date Revised 16.11.2017

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM149385234