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Ouabain activation of MAPK not dependent of caveolae: involvement on adherens junctions redistribution
Author(s) -
Barbosa Leandro A,
Souza Waldemir F,
Liu Lijun,
Fontes Carlos FL,
MorgadoDíaz José A
Publication year - 2013
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.27.1_supplement.726.2
Subject(s) - adherens junction , caveolae , ouabain , microbiology and biotechnology , caveolin 1 , mapk/erk pathway , chemistry , signal transduction , phosphorylation , cadherin , cell , biology , biochemistry , organic chemistry , sodium
Previous studies have reported that the Na,K‐ATPase interacts with E‐cadherin to stabilize adherens junctions (AJ) and maintain the cell‐cell adhesion. In the other hands, several papers have demonstrated that the activation of signaling pathway through the cardiotonic steroids is dependent of caveolin‐1 and caveolae. Here, we have used ouabain and Caco‐2 cells, a human colorectal cancer cell that not express caveolin‐1 and not develop caveolae. We have showed that ouabain treatment (6 and 8h) resulted in significant redistribution of AJ proteins, E‐cadherin and β‐catenin from the cell‐cell contacts to the cytoplasm, concomitantly with decreased protein levels of the β1Na,K‐ATPase. Besides, ouabain treatment induced an increase of the phosphorylation levels of ERK1/2 protein, and the treatment with PD98059, a specific MAPK inhibitor abrogated this effect. Additionally, the MAPK inhibitor blocked the effect of ouabain treatment on AJ disassembly, indicating that activation of this kinase was the final event in this signaling cascade. Our findings strongly suggest that downregulation of the β1 Na,K‐ATPase and MAPK activation induced by ouabain cooperate together to mediate cell‐cell adhesion loss in Caco‐2. Also, we have demonstrated that the modulation of Na,K‐ATPase signaling pathway can be independent of caveolin‐1 and caveolae content. Supported: CNPq, FAPERJ, FAPEMIG, CAPES