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

Autor(es)

Lucas, Thais F. G. ^[1] ; Amaral, Luciana S. ^[2] ; Porto, Catarina S. ^[1] ; Quintas, Luis E. M. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Farmacol, Setor Endocrinol Expt, Sao Paulo - Brazil

^[2] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Farmacol Bioquim & Mol, BR-21941902 Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Reproduction; v. 144, n. 6, p. 737-745, DEC 2012.
• Citações Web of Science: 15

Resumo

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 (AU)

• Processo FAPESP: 10/52306-8 - Receptores estrogênicos em células de Sertoli de ratos: importância para a espermatogênese
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Regular