PMID- 23774137
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20180815
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 73
DP  - 2013 Oct
TI  - Ouabain activates NFkappaB through an NMDA signaling pathway in cultured cerebellar 
      cells.
PG  - 327-36
LID - S0028-3908(13)00266-9 [pii]
LID - 10.1016/j.neuropharm.2013.06.006 [doi]
AB  - Na,K-ATPase, an ion pump, has been shown to interact with other proteins in 
      signaling complexes in cardiac myocytes, renal and glial cells, and several other 
      cell types. Our previous in vivo studies indicated that intrahippocampal 
      administration of ouabain (OUA), an inhibitor of Na,K-ATPase, induces NFkappaB 
      activation, leading to an increase in mRNA levels of target genes of this 
      transcription factor in the rat hippocampus. The present work investigated 
      whether OUA can regulate NF-kappaB in primary cultured rat cerebellar cells. Cells 
      were treated with different concentrations of OUA (1, 10 or 100 muM) for different 
      periods of time (1, 2 and 4 h). OUA induced a time- and concentration-dependent 
      activation of NFkappaB (peak of activation: 10 muM, 2 h), involving both p50/p65 and 
      p50/p50 NFkappaB dimers. OUA (10 muM, 2 h) induced upregulation of tumor necrosis 
      factor alpha (Tnf-alpha), interleukin-1beta (Il-1beta), and brain derived neurotrophic factor 
      (Bdnf) mRNA levels. Both NFkappaB activation and gene expression activation induced 
      by OUA (10 muM) were abolished when cells were pre-treated for 20 min with MK-801 
      (N-Methyl-D-Aspartate (NMDA) receptor antagonist), manumycin A 
      (farnesyltransferase inhibitor), PP-1(Src-family tyrosine kinase inhibitor) and 
      PD98059 (mitogen-activated protein kinase (MAPK) inhibitor). OUA (10 muM) alone or 
      in the presence of MK-801, PP-1, PD98059 did not cause cell death or DNA 
      fragmentation. These findings suggest that OUA activates NFkappaB by 
      NMDA-Src-Ras-like protein through MAPK pathways in cultured cerebellar cells. 
      This pathway may mediate an adaptive response in the central nervous system.
CI  - Published by Elsevier Ltd.
FAU - de Sa Lima, L
AU  - de Sa Lima L
AD  - Molecular Neuropharmacology Laboratory, Department of Pharmacology, Institute of 
      Biomedical Science, University of Sao Paulo, Sao Paulo 05508-900, Brazil. 
      limalarissa@yahoo.com.br
FAU - Kawamoto, E M
AU  - Kawamoto EM
FAU - Munhoz, C D
AU  - Munhoz CD
FAU - Kinoshita, P F
AU  - Kinoshita PF
FAU - Orellana, A M M
AU  - Orellana AM
FAU - Curi, R
AU  - Curi R
FAU - Rossoni, L V
AU  - Rossoni LV
FAU - Avellar, M C W
AU  - Avellar MC
FAU - Scavone, C
AU  - Scavone C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130615
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Flavonoids)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Polyenes)
RN  - 0 (Polyunsaturated Alkamides)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5ACL011P69 (Ouabain)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - OIQ298X4XD (manumycin)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cerebellum/*drug effects/metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Interleukin-1beta
MH  - NF-kappa B/*metabolism
MH  - Ouabain/antagonists & inhibitors/*pharmacology
MH  - Polyenes/pharmacology
MH  - Polyunsaturated Alkamides/pharmacology
MH  - Primary Cell Culture
MH  - Pyrazoles/pharmacology
MH  - Pyrimidines/pharmacology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/antagonists & inhibitors
MH  - Signal Transduction/*drug effects
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Bdnf
OT  - Il-1beta
OT  - NFkappaB
OT  - NMDA
OT  - OUA
OT  - Tnf-alpha
EDAT- 2013/06/19 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/06/19 06:00
PHST- 2012/05/25 00:00 [received]
PHST- 2013/06/01 00:00 [revised]
PHST- 2013/06/03 00:00 [accepted]
PHST- 2013/06/19 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - S0028-3908(13)00266-9 [pii]
AID - 10.1016/j.neuropharm.2013.06.006 [doi]
PST - ppublish
SO  - Neuropharmacology. 2013 Oct;73:327-36. doi: 10.1016/j.neuropharm.2013.06.006. 
      Epub 2013 Jun 15.