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Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC i...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856029/ https://www.ncbi.nlm.nih.gov/pubmed/20231377 http://dx.doi.org/10.1084/jem.20091704 |
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author | Tang, Zhongshu Arjunan, Pachiappan Lee, Chunsik Li, Yang Kumar, Anil Hou, Xu Wang, Bin Wardega, Piotr Zhang, Fan Dong, Lijin Zhang, Yongqing Zhang, Shi-Zhuang Ding, Hao Fariss, Robert N. Becker, Kevin G. Lennartsson, Johan Nagai, Nobuo Cao, Yihai Li, Xuri |
author_facet | Tang, Zhongshu Arjunan, Pachiappan Lee, Chunsik Li, Yang Kumar, Anil Hou, Xu Wang, Bin Wardega, Piotr Zhang, Fan Dong, Lijin Zhang, Yongqing Zhang, Shi-Zhuang Ding, Hao Fariss, Robert N. Becker, Kevin G. Lennartsson, Johan Nagai, Nobuo Cao, Yihai Li, Xuri |
author_sort | Tang, Zhongshu |
collection | PubMed |
description | Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions. |
format | Text |
id | pubmed-2856029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28560292010-10-12 Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation Tang, Zhongshu Arjunan, Pachiappan Lee, Chunsik Li, Yang Kumar, Anil Hou, Xu Wang, Bin Wardega, Piotr Zhang, Fan Dong, Lijin Zhang, Yongqing Zhang, Shi-Zhuang Ding, Hao Fariss, Robert N. Becker, Kevin G. Lennartsson, Johan Nagai, Nobuo Cao, Yihai Li, Xuri J Exp Med Article Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions. The Rockefeller University Press 2010-04-12 /pmc/articles/PMC2856029/ /pubmed/20231377 http://dx.doi.org/10.1084/jem.20091704 Text en © 2010 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Tang, Zhongshu Arjunan, Pachiappan Lee, Chunsik Li, Yang Kumar, Anil Hou, Xu Wang, Bin Wardega, Piotr Zhang, Fan Dong, Lijin Zhang, Yongqing Zhang, Shi-Zhuang Ding, Hao Fariss, Robert N. Becker, Kevin G. Lennartsson, Johan Nagai, Nobuo Cao, Yihai Li, Xuri Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation |
title | Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation |
title_full | Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation |
title_fullStr | Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation |
title_full_unstemmed | Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation |
title_short | Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation |
title_sort | survival effect of pdgf-cc rescues neurons from apoptosis in both brain and retina by regulating gsk3β phosphorylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856029/ https://www.ncbi.nlm.nih.gov/pubmed/20231377 http://dx.doi.org/10.1084/jem.20091704 |
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