PMID- 16524373
OWN - NLM
STAT- MEDLINE
DCOM- 20060518
LR  - 20230131
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 97
IP  - 1
DP  - 2006 Apr
TI  - Interactions between beta-neuregulin and neurotrophins in motor neuron apoptosis.
PG  - 222-33
AB  - Neuregulins play a major role in the formation and stabilization of neuromuscular 
      junctions, and are produced by both motor neurons and muscle. Although the 
      effects and mechanism of neuregulins on skeletal muscle (e.g. regulation of 
      acetylcholine receptor expression) have been studied extensively, the effects of 
      neuregulins on motor neurons remain unknown. We report that neuregulin-1beta 
      (NRGbeta1) inhibited apoptosis of rat motor neurons for up to 7 days in culture 
      by a phosphatidylinositol 3 kinase-dependent pathway and synergistically enhanced 
      motor neuron survival promoted by glial-derived neurotrophic factor (GDNF). 
      However, binding of neurotrophins, including brain-derived neurotrophic factor 
      (BDNF) and nerve growth factor (NGF), to the p75 neurotrophin receptor (p75NTR) 
      abolished the neuregulin anti-apoptotic effect on motor neurons. Inhibitors of 
      the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase prevented 
      motor neuron death caused by co-incubation of NRGbeta1 and BDNF or NGF, as well 
      as by trophic factor deprivation. Motor neuron apoptosis resulting from both 
      trophic factor deprivation and exposure to NRGbeta1 plus neurotrophins required 
      the induction of neuronal nitric oxide synthase and peroxynitrite formation. 
      Because motor neurons express both p75NTR and neuregulin erbB receptors during 
      the period of embryonic programmed cell death, motor neuron survival may be the 
      result of complex interactions between trophic and death factors, which may be 
      the same molecules acting in different combinations.
FAU - Ricart, Karina
AU  - Ricart K
AD  - Department of Physiology and Biophysics, The University of Alabama at Birmingham, 
      Birmingham, Alabama, USA.
FAU - J Pearson, Richard Jr
AU  - J Pearson R Jr
FAU - Viera, Liliana
AU  - Viera L
FAU - Cassina, Patricia
AU  - Cassina P
FAU - Kamaid, Andres
AU  - Kamaid A
FAU - Carroll, Steven L
AU  - Carroll SL
FAU - Estevez, Alvaro G
AU  - Estevez AG
LA  - eng
GR  - AG16582/AG/NIA NIH HHS/United States
GR  - NS36761/NS/NINDS NIH HHS/United States
GR  - NS37514/NS/NINDS NIH HHS/United States
GR  - NS42834/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060308
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuregulin-1)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (neuregulin beta)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Glial Cell Line-Derived Neurotrophic Factor/agonists/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Motor Neurons/drug effects/*metabolism
MH  - Nerve Growth Factor/metabolism/pharmacology
MH  - Nerve Growth Factors/*metabolism/pharmacology
MH  - Neuregulin-1/*metabolism/pharmacology
MH  - Nitric Oxide Synthase Type I/drug effects/metabolism
MH  - Peroxynitrous Acid/metabolism
MH  - Phosphatidylinositol 3-Kinases/drug effects/metabolism
MH  - Rats
MH  - Receptor, Nerve Growth Factor/agonists/metabolism
MH  - Spinal Cord/*embryology/*metabolism
EDAT- 2006/03/10 09:00
MHDA- 2006/05/19 09:00
CRDT- 2006/03/10 09:00
PHST- 2006/03/10 09:00 [pubmed]
PHST- 2006/05/19 09:00 [medline]
PHST- 2006/03/10 09:00 [entrez]
AID - JNC3739 [pii]
AID - 10.1111/j.1471-4159.2006.03739.x [doi]
PST - ppublish
SO  - J Neurochem. 2006 Apr;97(1):222-33. doi: 10.1111/j.1471-4159.2006.03739.x. Epub 
      2006 Mar 8.