PMID- 10428047
OWN - NLM
STAT- MEDLINE
DCOM- 19990813
LR  - 20211203
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 73
IP  - 2
DP  - 1999 Aug
TI  - Activation of phosphatidylinositol 3-kinase, but not extracellular-regulated 
      kinases, is necessary to mediate brain-derived neurotrophic factor-induced 
      motoneuron survival.
PG  - 521-31
AB  - Chick embryo spinal cord motoneurons develop a trophic response to some 
      neurotrophins when they are maintained in culture in the presence of muscle 
      extract. Thus, after 2 days in culture, brain-derived neurotrophic factor (BDNF) 
      promotes motoneuron survival. In the present study we have analyzed the 
      intracellular pathways that may be involved in the BDNF-induced motoneuron 
      survival. We have observed that BDNF activated the extracellular-regulated kinase 
      (ERK) mitogen-activated protein (MAP) kinase and the phosphatidylinositol (PI) 
      3-kinase pathways. To examine the contribution of these pathways to the survival 
      effect triggered by BDNF, we used PD 98059, a specific inhibitor of MAP kinase 
      kinase, and LY 294002, a selective inhibitor of PI 3-kinase. PD 98059, at doses 
      that significantly reduced the phosphorylation of ERKs, did not show any 
      prominent effect on neuronal survival. However, LY 294002 at doses that inhibited 
      the phosphorylation of Akt, a down-stream element of the PI 3-kinase, completely 
      abolished the motoneuron survival effects of BDNF. Moreover, cell death triggered 
      by LY 294002 treatment exhibited features similar to those observed after muscle 
      extract deprivation. Our results suggest that the PI 3-kinase pathway plays an 
      important role in the survival effect triggered by BDNF on motoneurons, whereas 
      activation of the ERK MAP kinase pathway is not relevant.
FAU - Dolcet, X
AU  - Dolcet X
AD  - Departament de Ciencies Mediques Basiques, Facultat de Medicina, Universitat de 
      Lleida, Catalonia, Spain.
FAU - Egea, J
AU  - Egea J
FAU - Soler, R M
AU  - Soler RM
FAU - Martin-Zanca, D
AU  - Martin-Zanca D
FAU - Comella, J X
AU  - Comella JX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Extracts)
RN  - 0 (Chromones)
RN  - 0 (Coumarins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (Oligopeptides)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 
      (benzyloxycarbonyl-aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Extracts/pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chick Embryo
MH  - Chromones/pharmacology
MH  - Coumarins/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Space/enzymology
MH  - Mitogen-Activated Protein Kinase 1
MH  - Morpholines/pharmacology
MH  - Motor Neurons/*cytology/drug effects/*enzymology
MH  - Muscle, Skeletal/enzymology
MH  - Oligopeptides/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1046/j.1471-4159.1999.0730521.x [doi]
PST - ppublish
SO  - J Neurochem. 1999 Aug;73(2):521-31. doi: 10.1046/j.1471-4159.1999.0730521.x.