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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-1-27
pubmed:abstractText
Excessive stimulation of the NMDA receptor induces neuronal cell death and is implicated in the development of several neurodegenerative diseases. While EGCG suppresses apoptosis induced by NMDA receptor-mediated excitotoxicity, the mechanisms underlying this process have yet to be completely determined. This study was designed to investigate whether (-)-epigallocatechin-3-gallate (EGCG) plays a neuroprotective role by inhibiting nitric oxide (NO) production and activating cellular signaling mechanisms including MAP kinase, PI3K, and GSK-3beta and acting on the antiapoptotic and the proapoptotic genes in N18D3 neural cells. The cells were pretreated with EGCG for 2 h and then exposed to quinolinic acid (QUIN), a NMDA receptor agonist, 30 mM for 24 h. MTT assay and DAPI staining were used to identify cell viability and apoptosis, respectively, and demonstrated that EGCG significantly increased cell viability and protected the cells from apoptotic death. In addition, EGCG had a capacity to reduce QUIN-induced excitotoxic cell death not only by blocking increase of intracellular calcium levels but also by inhibiting NO production. Gene expression analysis revealed that EGCG prevented the QUIN-induced expression of the proapoptotic gene, caspase-9, and increased that of the antiapoptotic genes, Bcl-XL, Bcl-2, and Bcl-w. Further examination about potential cell signaling candidate involved in this neuroprotective effect showed that immunoreacitivity of PI3K was significantly increased in the cells treated with EGCG. These results suggest that the neuroprotective mechanism of EGCG against QUIN-induced excitotoxic cell death includes regulation of PI3K and modulation of cell survival and death genes through decreasing of intracellular calcium levels and controlling of NO production.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
1313
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-33
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Neuroprotective effects of (-)-epigallocatechin-3-gallate against quinolinic acid-induced excitotoxicity via PI3K pathway and NO inhibition.
pubmed:affiliation
Department of Physiology, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't