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Article: PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis
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TitlePI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis
 
AuthorsCui, W3
Li, W3 2
Han, R3
Mak, S3
Zhang, H3
Hu, S3
Rong, J1
Han, Y3
 
KeywordsAkt
Apoptosis
ERK
Neuroprotection
Parkinson's disease
VEGF
 
Issue Date2011
 
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuint
 
CitationNeurochemistry International, 2011, v. 59 n. 6, p. 945-953 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuint.2011.07.005
 
AbstractVascular endothelial growth factor (VEGF), a specific pro-angiogenic peptide, has shown neuroprotective effects in the Parkinson's disease (PD) models, but the underlying mechanisms remain elusive. In this study, the neuroprotective properties of VEGF on 1-methyl-4-phenylpyridinium ion (MPP +)-induced neurotoxicity in primary cerebellar granule neurons were investigated. Pretreatment of VEGF prevented MPP +-induced neuronal apoptosis in a concentration- and time-dependent manner. And this prevention was blocked by PTK787/ZK222584, a VEGF receptor-2 specific inhibitor. Both inhibition of the Akt pathway and activation of the extracellular signal-regulated kinase (ERK) pathway contribute to MPP +-induced neuronal apoptosis. VEGF reversed the inhibition of phosphoinositide 3-kinase (PI3-K)/Akt pathway caused by MPP +, but further enhanced the activation of ERK induced by MPP +. Interestingly, VEGF and PD98059 (an ERK kinase inhibitor) play a synergistic role in protecting neurons from MPP +-induced toxicity. Collectively, these findings suggest that the PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis. This finding offers not only a new and clinically significant modality as to how VEGF exerts its neuroprotective effects but also a novel therapeutic strategy for PD by differentially regulating PD-associated signaling pathways. © 2011 Elsevier B.V. All rights reserved.
 
ISSN0197-0186
2012 Impact Factor: 2.659
2012 SCImago Journal Rankings: 0.980
 
DOIhttp://dx.doi.org/10.1016/j.neuint.2011.07.005
 
ISI Accession Number IDWOS:000297400700024
Funding AgencyGrant Number
Research Grants Council of Hong KongPolyU6608/07M
5609/09M
N_PolyU618/07
AoE/B15/01-II
Hong Kong Polytechnic UniversityG-YX96
G-YH19
Shenzhen Shuangbai Funding Scheme
Funding Information:

This work was supported by Grants from the Research Grants Council of Hong Kong (PolyU6608/07M, 5609/09M; N_PolyU618/07 and AoE/B15/01-II), The Hong Kong Polytechnic University (G-YX96 and G-YH19) and the Shenzhen Shuangbai Funding Scheme 2008. We sincerely thank Ms. Josephine Leung for proofreading our manuscript.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCui, W
 
dc.contributor.authorLi, W
 
dc.contributor.authorHan, R
 
dc.contributor.authorMak, S
 
dc.contributor.authorZhang, H
 
dc.contributor.authorHu, S
 
dc.contributor.authorRong, J
 
dc.contributor.authorHan, Y
 
dc.date.accessioned2011-08-26T14:41:10Z
 
dc.date.available2011-08-26T14:41:10Z
 
dc.date.issued2011
 
dc.description.abstractVascular endothelial growth factor (VEGF), a specific pro-angiogenic peptide, has shown neuroprotective effects in the Parkinson's disease (PD) models, but the underlying mechanisms remain elusive. In this study, the neuroprotective properties of VEGF on 1-methyl-4-phenylpyridinium ion (MPP +)-induced neurotoxicity in primary cerebellar granule neurons were investigated. Pretreatment of VEGF prevented MPP +-induced neuronal apoptosis in a concentration- and time-dependent manner. And this prevention was blocked by PTK787/ZK222584, a VEGF receptor-2 specific inhibitor. Both inhibition of the Akt pathway and activation of the extracellular signal-regulated kinase (ERK) pathway contribute to MPP +-induced neuronal apoptosis. VEGF reversed the inhibition of phosphoinositide 3-kinase (PI3-K)/Akt pathway caused by MPP +, but further enhanced the activation of ERK induced by MPP +. Interestingly, VEGF and PD98059 (an ERK kinase inhibitor) play a synergistic role in protecting neurons from MPP +-induced toxicity. Collectively, these findings suggest that the PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis. This finding offers not only a new and clinically significant modality as to how VEGF exerts its neuroprotective effects but also a novel therapeutic strategy for PD by differentially regulating PD-associated signaling pathways. © 2011 Elsevier B.V. All rights reserved.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationNeurochemistry International, 2011, v. 59 n. 6, p. 945-953 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuint.2011.07.005
 
dc.identifier.citeulike9564194
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuint.2011.07.005
 
dc.identifier.epage953
 
dc.identifier.hkuros194184
 
dc.identifier.isiWOS:000297400700024
Funding AgencyGrant Number
Research Grants Council of Hong KongPolyU6608/07M
5609/09M
N_PolyU618/07
AoE/B15/01-II
Hong Kong Polytechnic UniversityG-YX96
G-YH19
Shenzhen Shuangbai Funding Scheme
Funding Information:

This work was supported by Grants from the Research Grants Council of Hong Kong (PolyU6608/07M, 5609/09M; N_PolyU618/07 and AoE/B15/01-II), The Hong Kong Polytechnic University (G-YX96 and G-YH19) and the Shenzhen Shuangbai Funding Scheme 2008. We sincerely thank Ms. Josephine Leung for proofreading our manuscript.

 
dc.identifier.issn0197-0186
2012 Impact Factor: 2.659
2012 SCImago Journal Rankings: 0.980
 
dc.identifier.issue6
 
dc.identifier.openurl
 
dc.identifier.pmid21781996
 
dc.identifier.scopuseid_2-s2.0-80255135581
 
dc.identifier.spage945
 
dc.identifier.urihttp://hdl.handle.net/10722/138128
 
dc.identifier.volume59
 
dc.languageeng
 
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuint
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofNeurochemistry International
 
dc.relation.referencesReferences in Scopus
 
dc.subjectAkt
 
dc.subjectApoptosis
 
dc.subjectERK
 
dc.subjectNeuroprotection
 
dc.subjectParkinson's disease
 
dc.subjectVEGF
 
dc.titlePI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Emory University
  3. Hong Kong Polytechnic University