title: Ouabain and BDNF Crosstalk on Ganglion Cell Survival in Mixed Retinal Cell Cultures.
abstract: Brain-derived neurotrophic factor (BDNF) is a well-known and well-studied neurotrophin. Most biological effects of BDNF are mediated by the activation of TrkB receptors. This neurotrophin regulates several neuronal functions as cell proliferation, viability, and differentiation. Ouabain is a steroid that binds to the Na(+)/K(+) ATPase, inducing the activation of several intracellular signaling pathways. Previous data from our group described that ouabain treatment increases retinal ganglion cells survival (RGC). The aim of the present study was to evaluate, if this cardiac glycoside can have a synergistic effect with BDNF, the classical trophic factor for retinal ganglion cells, as well as investigate the intracellular signaling pathways involved. Our work demonstrated that the activation of Src, PLC, and PKCδ participates in the signaling cascade mediated by 50 ng/mL BDNF, since their selective inhibitors completely blocked the trophic effect of BDNF. We also demonstrated a synergistic effect on RGC survival when we concomitantly used ouabain (0.75 nM) and BDNF (10 ng/mL). Moreover, the signaling pathways involved in this synergistic effect include Src, PLC, PKCδ, and JNK. Our results suggest that the synergism between ouabain and BDNF occurs through the activation of the Src pathway, JNK, PLC, and PKCδ.
authors: Departamento de Neurobiologia, Programa de Neurociências, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Niterói, Rio de Janeiro, CEP 24020-140, Brazil, grcorrea@vm.uff.br.
authors: Gustavo
authors: G
authors: de Rezende Corrêa
authors: Vinicius Henrique Pedrosa
authors: VH
authors: Soares
authors: Leandro
authors: L
authors: de Araújo-Martins
authors: Aline Araujo
authors: AA
authors: Dos Santos
authors: Elizabeth
authors: E
authors: Giestal-de-Araujo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004357:Drug Synergism; D066246:ErbB Receptors / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010738:Type C Phospholipases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D010042:Ouabain; D066246:ErbB Receptors; D019061:src-Family Kinases; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D002118:Calcium
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