Study of the molecular mechanism activation of Wnt/Beta Catenin Signaling pathway by Ouabain in rat hippocampus.

Abstract

The Na +, K +-ATPase (Sodium Potassium Adenosine Trisfosfatase) is a highly conserved membrane protein in eukaryotes that establishes and maintains high intracellular concentrations of K+ and low Na+ through the hydrolysis of one ATP molecule. However, in addition to its regulatory role in ion homeostasis, studies suggest it's role in signal transduction and activation of gene transcription.In the presence of ouabain (OUA), an endogenous cardiotonic steroid, Na+, K+ - ATPase is able to promote intracellular Ca2+ levels oscillation and turn on the Src signaling pathway, with transactivation of the epidermal growth factor receptor (EGFR), and the MAPK signaling pathway (mitogen-activated protein kinase), which in turn can activate various transcription factors such as NF-kB (nuclear transcription factor kappa B). NFkB regulates the expression of genes that control programmed cell death, cell adhesion, proliferation, inflammation and tissue remodeling. Once activated, NFkB signaling pathway seems to modulate the activation of other signaling pathways, such as the canonical Wnt pathway (Wnt / Beta-catenin). Recently published data have shown that activation of EGF receptors may lead to transactivation of nuclear Beta-catenin, modulating the effector of the canonical Wnt pathway, without necessarily leading to activation of this pathway through its Frizzled receptor. Previous data from our laboratory showed that after 1 hour of OUA infusion, the NFkappaB signaling pathway is active, after 10 hours it can be seen an increase in phosphorylation ratio of GSK-3Beta protein, and after 24 hours there was an increase in nuclear translocation of Wnt/Beta-catenin. Thus, this project aims to determine the molecular mechanism of this modulation, since these pathways are intimately associated with the onset of neurodegenerative diseases, cancer and inflammatory processes.