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Article: PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis

TitlePI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosis
Authors
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
Citation
Neurochemistry International, 2011, v. 59 n. 6, p. 945-953 How to Cite?
Abstract
Vascular 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.
Persistent Identifierhttp://hdl.handle.net/10722/138128
ISSN
2013 Impact Factor: 2.650
2013 SCImago Journal Rankings: 1.251
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorCui, Wen_HK
dc.contributor.authorLi, Wen_HK
dc.contributor.authorHan, Ren_HK
dc.contributor.authorMak, Sen_HK
dc.contributor.authorZhang, Hen_HK
dc.contributor.authorHu, Sen_HK
dc.contributor.authorRong, Jen_HK
dc.contributor.authorHan, Yen_HK
dc.date.accessioned2011-08-26T14:41:10Z-
dc.date.available2011-08-26T14:41:10Z-
dc.date.issued2011en_HK
dc.identifier.citationNeurochemistry International, 2011, v. 59 n. 6, p. 945-953en_HK
dc.identifier.issn0197-0186en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138128-
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.en_HK
dc.languageengen_US
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuinten_HK
dc.relation.ispartofNeurochemistry Internationalen_HK
dc.subjectAkten_HK
dc.subjectApoptosisen_HK
dc.subjectERKen_HK
dc.subjectNeuroprotectionen_HK
dc.subjectParkinson's diseaseen_HK
dc.subjectVEGFen_HK
dc.titlePI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP +-induced neuronal apoptosisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0197-0186&volume=&spage=&epage=&date=2011&atitle=PI3-K/Akt+and+ERK+pathways+activated+by+VEGF+play+opposite+roles+in+MPP+-induced+neuronal+apoptosisen_US
dc.identifier.emailRong, J: jrong@hku.hken_HK
dc.identifier.authorityRong, J=rp00515en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.neuint.2011.07.005en_HK
dc.identifier.pmid21781996-
dc.identifier.scopuseid_2-s2.0-80255135581en_HK
dc.identifier.hkuros194184en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80255135581&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue6en_HK
dc.identifier.spage945en_HK
dc.identifier.epage953en_HK
dc.identifier.isiWOS:000297400700024-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridCui, W=35191650200en_HK
dc.identifier.scopusauthoridLi, W=35741086500en_HK
dc.identifier.scopusauthoridHan, R=13105830900en_HK
dc.identifier.scopusauthoridMak, S=35741097300en_HK
dc.identifier.scopusauthoridZhang, H=37762530600en_HK
dc.identifier.scopusauthoridHu, S=7404287697en_HK
dc.identifier.scopusauthoridRong, J=7005980047en_HK
dc.identifier.scopusauthoridHan, Y=8527680500en_HK
dc.identifier.citeulike9564194-

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