Activation of the low molecular weight protein tyrosine phosphatase in keratinocytes exposed to hyperosmotic stress

dc.contributor.authorSilva, Rodrigo A.
dc.contributor.authorPalladino, Marcelly V.
dc.contributor.authorCavalheiro, Renan P.
dc.contributor.authorMachado, Daisy
dc.contributor.authorCruz, Bread L. G.
dc.contributor.authorParedes-Gamero, Edgar J.
dc.contributor.authorGomes-Marcondes, Maria C. C.
dc.contributor.authorZambuzzi, Willian F. [UNESP]
dc.contributor.authorVasques, Luciana
dc.contributor.authorNader, Helena B.
dc.contributor.authorSouza, Ana Carolina S.
dc.contributor.authorJusto, Giselle Z.
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal do ABC (UFABC)
dc.date.accessioned2015-10-21T13:11:57Z
dc.date.available2015-10-21T13:11:57Z
dc.date.issued2015-03-17
dc.description.abstractHerein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH) and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.en
dc.description.affiliationUniv Estadual Campinas, Dept Bioquim, Inst Biol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Dept Quim &Bioquim, IBB, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Genet &Biol Evolut, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed ABC, Ctr Ciencias Nat &Humanas, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Dept Quim &Bioquim, IBB, Sao Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdFAPESP: 2006/07315-3
dc.description.sponsorshipIdCNPq: PQ-2
dc.format.extent1-19
dc.identifierhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119020
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 10, n. 3, p. 1-19, 2015.
dc.identifier.doi10.1371/journal.pone.0119020
dc.identifier.fileWOS000351284600044.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11449/128656
dc.identifier.wosWOS:000351284600044
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleActivation of the low molecular weight protein tyrosine phosphatase in keratinocytes exposed to hyperosmotic stressen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.author.orcid0000-0002-6435-6159[4]
unesp.author.orcid0000-0003-2229-6773[9]
unesp.author.orcid0000-0002-1713-756X[7]
unesp.author.orcid0000-0002-4149-5965[8]
unesp.author.orcid0000-0003-3686-8402[6]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt

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