Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/16816
Title: Preventing H2O2-induced apoptosis in cerebellar granule neurons by regulating the VEGFR-2/Akt signaling pathway using a novel dimeric antiacetylcholinesterase bis(12)-hupyridone
Authors: Cui, W
Li, W
Zhao, Y
Mak, S
Gao, Y
Luo, J
Zhang, H
Liu, Y
Carlier, PR
Rong, J
Han, Y 
Keywords: Bis(12)-hupyridone
Hydrogen peroxide
Neurodegenerative disorder
Oxidative stress
Vascular endothelial growth factor
Issue Date: 2011
Publisher: Elsevier
Source: Brain research, 2011, v. 1394, p. 14-23 How to cite?
Journal: Brain research 
Abstract: Oxidative stress-induced apoptosis plays a critical role in the pathogenesis of various neurodegenerative disorders. In this study, the neuroprotective properties of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase (AChE) inhibitor modified from a naturally occurring monomeric analogue, huperzine A, on H2O2-induced neurotoxicity were investigated in cerebellar granule neurons (CGNs). Exposure of CGNs to H2O2 resulted in apoptosis which could be attenuated by the pre-treatment of B12H (0.3-5 nM) in a concentration-dependent manner. Moreover, tacrine and neostigmine failed to prevent neurotoxicity, indicating that the neuroprotection of B12H might not be due to its inhibitory property of AChE enzymatic activity. Increased activation of extracellular signal-regulated kinase (ERK) and decreased activation of glycogen synthase kinase (GSK) 3β were observed after H2O2 exposure, and B12H reversed the altered activation of GSK3β, but not that of ERK. Furthermore, using vascular endothelial growth factor (VEGF), phospho-VEGF receptor-2 (VEGFR-2) antibody, a specific VEGFR-2 inhibitor (PTK787/ZK222584) and specific phosphoinositide 3-kinase inhibitors (LY294002 and wortmannin), it was found that VEGF prevented H2O2-induced neuronal loss from activating the VEGF/VEGFR-2 system and that the observed B12H neuroprotective effects might share the same signaling pathway. These findings strongly suggest that B12H prevents H2O2-induced neuronal apoptosis independent of inhibiting AChE, but through regulating VEGFR-2/Akt/GSK3β signaling pathway.
URI: http://hdl.handle.net/10397/16816
ISSN: 0006-8993
EISSN: 1872-6240
DOI: 10.1016/j.brainres.2011.02.006
Appears in Collections:Journal/Magazine Article

Access
View full-text via PolyU eLinks SFX Query
Show full item record

SCOPUSTM   
Citations

17
Last Week
0
Last month
0
Citations as of Dec 3, 2017

WEB OF SCIENCETM
Citations

17
Last Week
0
Last month
1
Citations as of Dec 9, 2017

Page view(s)

53
Last Week
0
Last month
Checked on Dec 10, 2017

Google ScholarTM

Check

Altmetric



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.