RGD Reference Report - Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-kappaB in the rat hippocampus. - Rat Genome Database

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Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-kappaB in the rat hippocampus.

Authors: Kawamoto, EM  Lima, LS  Munhoz, CD  Yshii, LM  Kinoshita, PF  Amara, FG  Pestana, RR  Orellana, AM  Cipolla-Neto, J  Britto, LR  Avellar, MC  Rossoni, LV  Scavone, C 
Citation: Kawamoto EM, etal., J Neurosci Res. 2011 Oct 18. doi: 10.1002/jnr.22745.
RGD ID: 5508715
Pubmed: PMID:22006678   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.22745   (Journal Full-text)

It has been shown that ouabain (OUA) can activate the Na,K-ATPase complex and mediate intracellular signaling in the central nervous system (CNS). Inflammatory stimulus increases glutamatergic transmission, especially at N-methyl-D-aspartate (NMDA) receptors, which are usually coupled to the activation of nitric oxide synthase (NOS). Nuclear factor-kappaB (NF-kappaB) activation modulates the expression of genes involved in development, plasticity, and inflammation. The present work investigated the effects of OUA on NF-kappaB binding activity in rat hippocampus and the influence of this OUA-Na,K-ATPase signaling cascade in NMDA-mediated NF-kappaB activation. The findings presented here are the first report indicating that intrahippocampal administration of OUA, in a concentration that did not alter Na,K-ATPase or NOS activity, induced an activation of NF-kappaB, leading to increases in brain-derived neurotrophic factor (Bdnf), inducible NOS (iNos), tumor necrosis factor-alpha (Tnf-alpha), and B-cell leukemia/lymphoma 2 (Bcl2) mRNA levels. This response was not linked to any significant signs of neurodegeneration as showed via Fluoro-Jade B and Nissl stain. Intrahippocampal administration of NMDA induced NF-kappaB activation and increased NOS and alpha(2/3) -Na,K-ATPase activities. NMDA treatment further increased OUA-induced NF-kappaB activation, which was partially blocked by MK-801, an antagonist of NMDA receptor. These results suggest that OUA-induced NF-kappaB activation is at least in part dependent on Na,K-ATPase modulatory action of NMDA receptor in hippocampus. The interaction of these signaling pathways could be associated with biological mechanisms that may underlie the basal homeostatic state linked to the inflammatory signaling cascade in the brain. (c) 2011 Wiley-Liss, Inc.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glycoside metabolic process  IEP 5508715ouabainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)


Additional Information