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

• Autor(a) principal: Lucas, Thais Fabiana Gameiro [UNIFESP]
• Data de Publicação: 2012
• Outros Autores: Amaral, Luciana Silva do, Porto, Catarina Segreti [UNIFESP], Quintas, Luis Eduardo Menezes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://repositorio.unifesp.br/handle/11600/35533; https://dx.doi.org/10.1530/REP-12-0232

Novel 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) 144 737-745