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Platelet-derived gr...
Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1.
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Peng, Fuwang (author)
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Yao, Honghong (author)
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Bai, Xuetao (author)
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Zhu, Xuhui (author)
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Reiner, Benjamin C (author)
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Beazely, Michael (author)
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- Funa, Keiko, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Xiong, Huangui (author)
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Buch, Shilpa (author)
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(creator_code:org_t)
- 2010
- 2010
- English.
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In: The Journal of biological chemistry. - 1083-351X. ; 285:28, s. 21615-24
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https://doi.org/10.1...
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Abstract
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- Platelet-derived growth factor (PDGF) is a pleiotropic protein with critical roles in both developmental as well as pathogenic processes. In the central nervous system specifically, PDGF is critical for neuronal proliferation and differentiation and has also been implicated as a neuroprotective agent. Whether PDGF also plays a role in synaptic plasticity, however, remains poorly understood. In the present study we demonstrated that in the rat hippocampal neurons PDGF regulated the expression of Arc/Arg3.1 gene that has been implicated in both synapse plasticity and long term potentiation. Relevance of these findings was further confirmed in vivo by injecting mice with intracerebral inoculations of PDGF, which resulted in a rapid induction of Arc in the hippocampus of the injected mice. PDGF induced long term potentiation in rat hippocampal slices, which was abolished by PDGF receptor-tyrosine kinase inhibitor STI-571. We also present evidence that PDGF-mediated induction of Arc/Arg3.1 involved activation of the MAPK/ERK (MEK) pathway. Additionally, induction of Arc/Arg3.1 also involved the upstream release of intracellular calcium stores, an effect that could be blocked by thapsigargin but not by EGTA. Pharmacological approach using inhibitors specific for either MAPK/ERK phosphorylation or calcium release demonstrated that the two pathways converged downstream at a common point involving activation of the immediate early gene Egr-1. Chromatin immunoprecipitation assays demonstrated the binding of Egr-1, but not Egr-3, to the Arc promoter. These findings for the first time, thus, suggest an additional role of PDGF, that of induction of Arc.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Animals
- Calcium
- metabolism
- Cell Proliferation
- Cytoskeletal Proteins
- metabolism
- Electrophysiology
- Enzyme Activation
- Female
- Gene Expression Regulation
- Hippocampus
- metabolism
- MAP Kinase Signaling System
- Mice
- Mice
- Inbred C57BL
- Nerve Growth Factors
- metabolism
- Nerve Tissue Proteins
- metabolism
- Phosphatidylinositol 3-Kinases
- Platelet-Derived Growth Factor
- metabolism
- Rats
- Rats
- Sprague-Dawley
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Peng, Fuwang
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Yao, Honghong
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Bai, Xuetao
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Zhu, Xuhui
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Reiner, Benjamin ...
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Beazely, Michael
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show more...
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Funa, Keiko, 194 ...
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Xiong, Huangui
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Buch, Shilpa
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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The Journal of b ...
- By the university
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University of Gothenburg