PMID- 25892444
OWN - NLM
STAT- MEDLINE
DCOM- 20160323
LR  - 20150606
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 411
DP  - 2015 Aug 15
TI  - Melanocortin 4 receptor activates ERK-cFos pathway to increase brain-derived 
      neurotrophic factor expression in rat astrocytes and hypothalamus.
PG  - 28-37
LID - S0303-7207(15)00194-X [pii]
LID - 10.1016/j.mce.2015.04.008 [doi]
AB  - Melanocortins are neuropeptides with well recognized anti-inflammatory and 
      anti-apoptotic effects in the brain. Of the five melanocortin receptors (MCR), 
      MC4R is abundantly expressed in the brain and is the only MCR present in 
      astrocytes. We have previously shown that MC4R activation by the alpha-melanocyte 
      stimulating hormone (alpha-MSH) analog, NDP-MSH, increased brain-derived neurotrophic 
      factor (BDNF) expression through the classic cAMP-Protein kinase A-cAMP 
      responsive element binding protein pathway in rat astrocytes. Now, we examined 
      the participation of the mitogen activated protein kinases pathway in MC4R 
      signaling. Rat cultured astrocytes treated with NDP-MSH 1 microM for 1 h showed 
      increased BDNF expression. Inhibition of extracellular signal-regulated kinase 
      (ERK) and ribosomal p90 S6 kinase (RSK), an ERK substrate, but not of p38 or JNK, 
      prevented the increase in BDNF expression induced by NDP-MSH. Activation of MC4R 
      increased cFos expression, a target of both ERK and RSK. ERK activation by MC4R 
      involves cAMP, phosphoinositide-3 kinase (PI3K) and the non receptor tyrosine 
      kinase, Src. Both PI3K and Src inhibition abolished NDP-MSH-induced BDNF 
      expression. Moreover, we found that intraperitoneal injection of alpha-MSH induces 
      BDNF and MC4R expression and activates ERK and cFos in male rat hypothalamus. Our 
      results show for the first time that MC4R-induced BDNF expression in astrocytes 
      involves ERK-RSK-cFos pathway which is dependent on PI3K and Src, and that 
      melanocortins induce BDNF expression and ERK-cFos activation in rat hypothalamus.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Ramirez, D
AU  - Ramirez D
AD  - INBIOMED UBA-CONICET, School of Medicine, University of Buenos Aires, Buenos 
      Aires, Argentina.
FAU - Saba, J
AU  - Saba J
AD  - INBIOMED UBA-CONICET, School of Medicine, University of Buenos Aires, Buenos 
      Aires, Argentina.
FAU - Carniglia, L
AU  - Carniglia L
AD  - INBIOMED UBA-CONICET, School of Medicine, University of Buenos Aires, Buenos 
      Aires, Argentina.
FAU - Durand, D
AU  - Durand D
AD  - INBIOMED UBA-CONICET, School of Medicine, University of Buenos Aires, Buenos 
      Aires, Argentina.
FAU - Lasaga, M
AU  - Lasaga M
AD  - INBIOMED UBA-CONICET, School of Medicine, University of Buenos Aires, Buenos 
      Aires, Argentina.
FAU - Caruso, C
AU  - Caruso C
AD  - INBIOMED UBA-CONICET, School of Medicine, University of Buenos Aires, Buenos 
      Aires, Argentina. Electronic address: ccaruso@fmed.uba.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150416
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Receptor, Melanocortin, Type 4)
RN  - 581-05-5 (alpha-MSH)
RN  - 75921-69-6 (MSH, 4-Nle-7-Phe-alpha-)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Hypothalamus/drug effects/*metabolism
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-fos/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Melanocortin, Type 4/*metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - alpha-MSH/analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - Astrocytes
OT  - BDNF
OT  - ERK
OT  - Hypothalamus
OT  - MC4R
OT  - cFos
EDAT- 2015/04/22 06:00
MHDA- 2016/03/24 06:00
CRDT- 2015/04/21 06:00
PHST- 2014/12/15 00:00 [received]
PHST- 2015/04/09 00:00 [revised]
PHST- 2015/04/09 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
AID - S0303-7207(15)00194-X [pii]
AID - 10.1016/j.mce.2015.04.008 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2015 Aug 15;411:28-37. doi: 10.1016/j.mce.2015.04.008. Epub 
      2015 Apr 16.