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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2009-6-18
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pubmed:abstractText |
Fibroblast growth factor-2 (FGF-2) is predominantly synthesized and secreted by astrocytes in adult brain. Our previous study showed that activation of classical dopamine receptor D(1) or D(2) elicits FGF-2 biosynthesis and secretion in astrocytes. Here, we report that astrocytic FGF-2 expression is also regulated by phosphatidylinositol (PI)-linked D(1)-like receptor. SKF83959, a selective PI-linked D(1)-like receptor agonist, upregulates the levels of FGF-2 protein in striatal astrocyte cultures in classical dopamine D(1) and D(2) receptor-independent manner. The conditional medium derived from SKF83959-activated astrocytes promoted the number of TH(+) neurons in vitro. Treatment of astrocytes with SKF83959 increased intracellular calcium in two phases. Inhibition of intracellular calcium oscillation by inositol 1,4,5-triphosphate (IP3) inhibitors blocked the SKF83959-induced increase in FGF-2 expression. Moreover, intraperitoneal administration of SKF83959 reversed l-methyl-4-phenyl-l,2,3,6-tetrahydropypridine (MPTP)-induced reduction in FGF-2 expression in both the striatum and ventral midbrain and resulted in marked protection of dopaminergic neurons from MPTP-induced neurotoxicity. These results indicate that IP3/Ca(2+)/calmodulin-dependent protein kinase is an uncharted intracellular signaling pathway that is crucial for the regulation of FGF-2 synthesis in astrocytes. PI-linked D(1)-like receptor plays an important role in the regulation of astrocytic FGF-2 expression and neuroprotection which may provide a potential target for the drug discovery in Parkinson's disease.
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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/1-Methyl-4-phenyl-1,2,3,6-tetrahydro...,
http://linkedlifedata.com/resource/pubmed/chemical/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-p...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1,
http://linkedlifedata.com/resource/pubmed/chemical/SCH 23390,
http://linkedlifedata.com/resource/pubmed/chemical/SK&F 83959,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
17
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7766-75
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pubmed:meshHeading |
pubmed-meshheading:19535588-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine,
pubmed-meshheading:19535588-2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine,
pubmed-meshheading:19535588-Animals,
pubmed-meshheading:19535588-Animals, Newborn,
pubmed-meshheading:19535588-Astrocytes,
pubmed-meshheading:19535588-Benzazepines,
pubmed-meshheading:19535588-Calcium Signaling,
pubmed-meshheading:19535588-Cells, Cultured,
pubmed-meshheading:19535588-Culture Media, Conditioned,
pubmed-meshheading:19535588-Dopamine Agonists,
pubmed-meshheading:19535588-Dopamine Antagonists,
pubmed-meshheading:19535588-Dose-Response Relationship, Drug,
pubmed-meshheading:19535588-Drug Interactions,
pubmed-meshheading:19535588-Embryo, Mammalian,
pubmed-meshheading:19535588-Enzyme Inhibitors,
pubmed-meshheading:19535588-Fibroblast Growth Factor 2,
pubmed-meshheading:19535588-Gene Expression Regulation,
pubmed-meshheading:19535588-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:19535588-Mesencephalon,
pubmed-meshheading:19535588-Mice,
pubmed-meshheading:19535588-Mice, Inbred C57BL,
pubmed-meshheading:19535588-Neurons,
pubmed-meshheading:19535588-Neurotoxins,
pubmed-meshheading:19535588-Phosphatidylinositols,
pubmed-meshheading:19535588-Rats,
pubmed-meshheading:19535588-Rats, Sprague-Dawley,
pubmed-meshheading:19535588-Receptors, Dopamine D1,
pubmed-meshheading:19535588-Tyrosine 3-Monooxygenase
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pubmed:year |
2009
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pubmed:articleTitle |
Activation of phosphatidylinositol-linked D1-like receptor modulates FGF-2 expression in astrocytes via IP3-dependent Ca2+ signaling.
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pubmed:affiliation |
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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