Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/24462
Title: PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP+-induced neuronal apoptosis
Authors: Cui, W
Li, W
Han, R
Mak, S
Zhang, H
Hu, S
Rong, J
Han, Y 
Keywords: Akt
Apoptosis
ERK
Neuroprotection
Parkinson's disease
VEGF
Issue Date: 2011
Publisher: Pergamon-Elsevier Science Ltd
Source: Neurochemistry international, 2011, v. 59, no. 6, p. 945-953 How to cite?
Journal: Neurochemistry International 
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.
URI: http://hdl.handle.net/10397/24462
DOI: 10.1016/j.neuint.2011.07.005
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