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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-7-2
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pubmed:abstractText |
FGF-2 is a potent neurotrophic factor for several populations of CNS neurons and has been shown to protect hippocampal neurons from glutamate-induced cell death in vitro and in vivo. Mechanisms underlying the neurotrophic and protective actions of FGF-2 have been resolved only in part. Using glutamate-treated cultured hippocampal neurons we show that FGF-2 shares its neuroprotective capacity with GDNF. Hippocampal neurons express glial-cell-line-derived neurotrophic factor (GDNF), its receptors c-Ret and the lipid-anchored GDNF family receptor-alpha1 (GFRalpha-1), and the FGF receptor 1 (FGFR I). Neutralizing antibodies to GDNF abolish the neuroprotective effect of FGF-2. In support of the notion that GDNF is required to permit the protective effects of FGF-2 we find that FGF-2 up-regulates GDNF and GFRalpha-1 in hippocampal neurons. Furthermore, FGF-2-induced GDNF causes enhanced phosphorylation of c-Ret and the signaling components Akt and Erk. A putative downstream target of FGF-2 and GDNF are bcl-2 gene family members, whose mRNAs are differentially up-regulated by the two factors. Together, these data suggest that GDNF is an important protective factor for glutamate-lesioned hippocampal neurons and an essential mediator of the neuroprotective actions of FGF-2.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Gfra1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ret oncogene protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Ret protein, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1044-7431
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2002 Elsevier Science (USA).
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
181-97
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12093153-Animals,
pubmed-meshheading:12093153-Antibodies,
pubmed-meshheading:12093153-Apoptosis,
pubmed-meshheading:12093153-Brain Ischemia,
pubmed-meshheading:12093153-Cell Death,
pubmed-meshheading:12093153-Cells, Cultured,
pubmed-meshheading:12093153-Cytokines,
pubmed-meshheading:12093153-Drosophila Proteins,
pubmed-meshheading:12093153-Drug Interactions,
pubmed-meshheading:12093153-Female,
pubmed-meshheading:12093153-Fetus,
pubmed-meshheading:12093153-Fibroblast Growth Factor 2,
pubmed-meshheading:12093153-Gene Expression Regulation,
pubmed-meshheading:12093153-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:12093153-Glial Cell Line-Derived Neurotrophic Factor Receptors,
pubmed-meshheading:12093153-Glutamic Acid,
pubmed-meshheading:12093153-Hippocampus,
pubmed-meshheading:12093153-Membrane Microdomains,
pubmed-meshheading:12093153-Nerve Growth Factors,
pubmed-meshheading:12093153-Nerve Tissue Proteins,
pubmed-meshheading:12093153-Neurons,
pubmed-meshheading:12093153-Neuroprotective Agents,
pubmed-meshheading:12093153-Phosphorylation,
pubmed-meshheading:12093153-Pregnancy,
pubmed-meshheading:12093153-Proto-Oncogene Proteins,
pubmed-meshheading:12093153-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:12093153-RNA, Messenger,
pubmed-meshheading:12093153-Rats,
pubmed-meshheading:12093153-Rats, Wistar,
pubmed-meshheading:12093153-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:12093153-Signal Transduction
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pubmed:year |
2002
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pubmed:articleTitle |
Fibroblast growth factor-2 requires glial-cell-line-derived neurotrophic factor for exerting its neuroprotective actions on glutamate-lesioned hippocampal neurons.
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pubmed:affiliation |
Department of Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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