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dc.contributor.authorLima, Bruno Bezerra-
dc.contributor.authorFonseca, Bárbara Faria-
dc.contributor.authorAmado, Nathália da Graça-
dc.contributor.authorLima, Débora Moreira-
dc.contributor.authorRibeiro, Ronaldo Albuquerque-
dc.contributor.authorAbreu, José Garcia-
dc.contributor.authorBrito, Gerly Anne de Castro-
dc.date.accessioned2015-05-19T13:43:52Z-
dc.date.available2015-05-19T13:43:52Z-
dc.date.issued2014-07-
dc.identifier.citationLIMA, B. B. et al. Clostridium difficile Toxin A attenuates Wnt/B-Catenin signaling in intestinal epithelial cells. Infection and Immunity, Washington, v. 82, n. 7, p. 2680–2687, jul. 2014.pt_BR
dc.identifier.issn1098-5522 Online-
dc.identifier.urihttp://www.repositorio.ufc.br/handle/riufc/12280-
dc.language.isoenpt_BR
dc.publisherInfection and Immunitypt_BR
dc.subjectClostridium difficilept_BR
dc.subjectCélulas Epiteliaispt_BR
dc.titleClostridium difficile toxin A attenuates Wnt/B-Catenin signaling in intestinal epithelial cellspt_BR
dc.typeArtigo de Periódicopt_BR
dc.description.abstract-ptbrClostridium difficile toxins A and B (TcdA and TcdB) are homologous glycosyltransferases that inhibit a group of small GTPases within host cells, but several mechanisms underlying their pathogenic activity remain unclear. In this study, we evaluated the effects of TcdA on the Wnt/ -catenin pathway, the major driving force behind the proliferation of epithelial cells in colonic crypts. IEC-6 and RKO cells stimulated with Wnt3a-conditioned medium were incubated with 10, 50, and 100 ng/ml of TcdA for 24 h, resulting in a dose-dependent inhibition of the Wnt signaling, as demonstrated by a T-cell factor (TCF) reporter assay. This was further confirmed by immunofluorescence staining for nuclear localization of -catenin and Western blotting for -catenin and c-Myc (encoded by a Wnt target gene). Moreover, our Western blot analysis showed a decrease in the -catenin protein levels, which was reversed by z-VAD-fmk, a pan-caspase inhibitor. Nonetheless, TcdA was still able to inhibit the Wnt/ -catenin pathway even in the presence of z-VAD-fmk, lithium chloride (a GSK3 inhibitor), or constitutively active -catenin, as determined by a TCF reporter assay. Furthermore, preincubation of RKO cells with TcdA for 12 h also attenuated Wnt3a-mediated activation of Wnt signaling, suggesting that inactivation of Rho GTPases plays a significant role in that inhibition. Taken together, these findings suggest that attenuation of the Wnt signaling by TcdA is important for TcdA antiproliferative effects.pt_BR
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