PI3K-ERK1/2 activation contributes to extracellular H2O2 generation in amyloid beta toxicity

Cited 10 time in scopus
Metadata Downloads
Title
PI3K-ERK1/2 activation contributes to extracellular H2O2 generation in amyloid beta toxicity
Author(s)
Jong Seong Ha; Hye Yeong Sung; H M Lim; Ki Sun KwonSung Sup Park
Bibliographic Citation
Neuroscience Letters, vol. 526, no. 2, pp. 112-117
Publication Year
2012
Abstract
Amyloid β peptide (Aβ) induces hydrogen peroxide (H2O2) and superoxide generation, leading to neuronal death. Many studies have shown the involvement of NADPH oxidase, but the isotype-specific role was not assessed. Moreover, the activation status of phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) 1/2 is unclear in extracellular H2O2 generation. In this paper, we showed that Aβ1-42 induced extracellular H2O2 generation and the resulting cytotoxicity in a concentration-dependent manner. Nox2- and Nox4-specific siRNAs suppressed H2O2 and superoxide generation. LY294002 and U0126, inhibitors of PI3K and ERK1/2, respectively, reduced H2O2 generation in concentration-dependent manners. Furthermore, PI3K activation is responsible for ERK1/2 phosphorylation. An additional increase in H2O2 generation and corresponding cytotoxicity was observed after treatment with Aβ1-42 and glutamate. These results suggest that Aβ1-42 enhances the neuronal vulnerability to oxidative injury in Alzheimer's disease (AD) by increasing H2O2 generation.
Keyword
Amyloid peptideOxidative stressNADPH oxidasePI3KERK1/2
ISSN
0304-3940
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.neulet.2012.08.023
Type
Article
Appears in Collections:
Division of Research on National Challenges > Aging Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.