期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 25, 页码 11387-11392出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1000500107
关键词
claudins; c-Src; ERK1/2; Madin-Darby canine kidney; occludin
资金
- National Research Council of Mexico
- Instituto de Ciencia y Tecnologia del Distrito Federal
- Medical Research Council [G0700743] Funding Source: researchfish
- MRC [G0700743] Funding Source: UKRI
Epithelial cells treated with high concentrations of ouabain (e.g., 1 mu M) retrieve molecules involved in cell contacts from the plasma membrane and detach from one another and their substrates. On the basis of this observation, we suggested that ouabain might also modulate cell contacts at low, nontoxic levels (10 or 50 nM). To test this possibility, we analyzed its effect on a particular type of cell-cell contact: the tight junction (TJ). We demonstrate that at concentrations that neither inhibit K+ pumping nor disturb the K+ balance of the cell, ouabain modulates the degree of sealing of the TJ as measured by transepithelial electrical resistance (TER) and the flux of neutral 3 kDa dextran (J(DEX)). This modulation is accompanied by changes in the levels and distribution patterns of claudins 1, 2, and 4. Interestingly, changes in TER, J(DEX), and claudins behavior are mediated through signal pathways containing ERK1/2 and c-Src, which have distinct effects on each physiological parameter and claudin type. These observations support the theory that at low concentrations, ouabain acts as a modulator of cell-cell contacts.
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