Na+/K+-ATPase alpha 1 isoform mediates ouabain-induced expression of cyclin D1 and proliferation of rat Sertoli cells

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dc.contributor.authorLucas, Thais Fabiana Gameiro [UNIFESP]
dc.contributor.authorAmaral, Luciana Silva do
dc.contributor.authorPorto, Catarina Segreti [UNIFESP]
dc.contributor.authorQuintas, Luis Eduardo Menezes
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:28:03Z
dc.date.available2016-01-24T14:28:03Z
dc.date.issued2012-12-01
dc.description.abstractNovel roles for the interaction of cardiotonic steroids to Na+/K+-ATPase have been established in recent years. the aim of this study was to investigate the intracellular signaling events downstream the action of ouabain on Na+/K+-ATPase in Sertoli cell obtained from immature rats. Treatment of Sertoli cells with ouabain (1 mu M) induced a rapid and transient increase in the extracellular signal-regulated kinase (ERK1/2 or MAPK3/1) and phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) phosphorylation. Also, ouabain upregulated the expression of cyclin D1 and incorporation of [methyl-H-3]thymidine, both of which were dependent on MAPK3/1 but not AKT intracellular cascade, as shown by pretreatment with MEK (MAP2K1/2) inhibitor U0126 and PI3K inhibitor wortmannin respectively. Moreover, the effect of ouabain on these proliferation parameters was completely prevented by phospho-cAMP response element-binding protein (CREB)/CREB-binding protein complex inhibitor KG501 and only partially by nuclear factor kappa B nuclear translocation inhibitor SN50. Pretreatment with estrogen receptor antagonist ICI 182 780 showed that MAPK3/1 activation by ouabain does not involve this receptor. the Na+/K+-ATPase alpha 1 isoform, but not alpha 4, was detected in Sertoli cells, suggesting that ouabain effects in Sertoli cells are mediated via alpha 1. Taken together, these results show a rapid ouabain action in the Sertoli cells, which in turn can modulate nuclear transcriptional events essential for Sertoli cell proliferation in a critical period of testicular development. Our findings are important to understand the role of ouabain in the testis and its possible implications in male infertility. Reproduction (2012) 144 737-745en
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Farmacol Bioquim & Mol, BR-21941902 Rio de Janeiro, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, Setor Endocrinol Expt, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, Setor Endocrinol Expt, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)pt
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt
dc.description.sponsorshipIDFAPESP: 2010/52306-8pt
dc.description.sponsorshipIDFAPERJ: E-26/110.370/2010pt
dc.format.extent737-745
dc.identifierhttps://dx.doi.org/10.1530/REP-12-0232
dc.identifier.citationReproduction. Bristol: Bioscientifica Ltd, v. 144, n. 6, p. 737-745, 2012.
dc.identifier.doi10.1530/REP-12-0232
dc.identifier.issn1470-1626
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/35533
dc.identifier.wosWOS:000311702300009
dc.language.isoeng
dc.publisherBioscientifica Ltd
dc.relation.ispartofReproduction
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleNa+/K+-ATPase alpha 1 isoform mediates ouabain-induced expression of cyclin D1 and proliferation of rat Sertoli cellsen
dc.typeinfo:eu-repo/semantics/article
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