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• W2076602201 endingPage "378" @default.
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• W2076602201 abstract "Cadherins are a family of transmembrane glycoproteins mediating calcium-dependent, homophilic cell-cell adhesion. In addition, these molecules are involved in signaling events, regulating such processes as cell motility, proliferation, and apoptosis. Members of the cadherin subfamily, called either classical or type I cadherins, contain a highly conserved sequence at their homophilic binding site consisting of the three amino acids--histidine-alanine-valine (HAV). Previous studies have shown that peptides containing the HAV motif inhibit cadherin-dependent events such as cell aggregation, compaction, and neurite outgrowth. We report here that a cyclic peptide, N-Ac-CHAVC-NH2 can perturb cadherin-mediated endothelial cell interactions, resulting in a progressive apoptotic cell death. This effect depends on cell density, as it is only observed when dense cultures are treated with the peptide. Adherens junction (AJ)-associated cadherin and catenins are differentially affected by the N-Ac-CHAVC-NH2 treatment, as judged by double immunofluorescence labeling followed by immunofluorescence-ratio imaging. However, cell-cell adhesions are largely retained during the first few hours after addition of the peptide. It was also observed that following treatment, actin filaments partially lose their plasma membrane anchorage at AJs and translocate towards the cell center. Interestingly, addition of basic fibroblast growth factor to confluent, peptide-treated, endothelial cell cultures, completely blocks apoptosis and the inhibitory peptide reduce the phosphorylation of the FGF receptor target protein FRS2, suggesting that the peptide exerts its effect by inhibiting cadherin-mediated activation of fibroblast growth factor receptor signaling. We propose that cadherin-mediated signaling is essential for maintaining viability of confluent endothelial cells, and that its perturbation by N-Ac-CHAVC-NH2 drives these cells to apoptosis." @default.
• W2076602201 created "2016-06-24" @default.
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• W2076602201 date "2004-04-01" @default.
• W2076602201 modified "2023-10-16" @default.
• W2076602201 title "Induction of apoptosis in cultured endothelial cells by a cadherin antagonist peptide: involvement of fibroblast growth factor receptor-mediated signalling" @default.
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• W2076602201 doi "https://doi.org/10.1016/j.yexcr.2003.11.033" @default.
• W2076602201 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15023527" @default.
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