PMID- 25651946
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20181203
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 35
IP  - 5
DP  - 2015 Jul
TI  - Ouabain and BDNF Crosstalk on Ganglion Cell Survival in Mixed Retinal Cell 
      Cultures.
PG  - 651-60
LID - 10.1007/s10571-015-0160-3 [doi]
AB  - 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 PKCdelta 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, PKCdelta, and JNK. Our 
      results suggest that the synergism between ouabain and BDNF occurs through the 
      activation of the Src pathway, JNK, PLC, and PKCdelta.
FAU - de Rezende Correa, Gustavo
AU  - de Rezende Correa G
AD  - Departamento de Neurobiologia, Programa de Neurociencias, Instituto de Biologia, 
      Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/n, Niteroi, Rio de 
      Janeiro, CEP 24020-140, Brazil, grcorrea@vm.uff.br.
FAU - Soares, Vinicius Henrique Pedrosa
AU  - Soares VH
FAU - de Araujo-Martins, Leandro
AU  - de Araujo-Martins L
FAU - Dos Santos, Aline Araujo
AU  - Dos Santos AA
FAU - Giestal-de-Araujo, Elizabeth
AU  - Giestal-de-Araujo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150205
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (NF-kappa B)
RN  - 5ACL011P69 (Ouabain)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Drug Synergism
MH  - ErbB Receptors/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Ouabain/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C-delta/metabolism
MH  - Rats
MH  - Retinal Ganglion Cells/*cytology/drug effects/enzymology
MH  - Type C Phospholipases/metabolism
MH  - src-Family Kinases/metabolism
EDAT- 2015/02/06 06:00
MHDA- 2016/03/29 06:00
CRDT- 2015/02/06 06:00
PHST- 2014/10/28 00:00 [received]
PHST- 2015/01/27 00:00 [accepted]
PHST- 2015/02/06 06:00 [entrez]
PHST- 2015/02/06 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
AID - 10.1007/s10571-015-0160-3 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2015 Jul;35(5):651-60. doi: 10.1007/s10571-015-0160-3. Epub 
      2015 Feb 5.