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Inhibition of cPLA 2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress‐induced cell death
Author(s) -
Zhao Zhen,
Liu Naikui,
Huang Jingya,
Lu PeiHua,
Xu XiaoMing
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07160.x
Subject(s) - neuroprotection , excitotoxicity , ginkgo biloba , glutamate receptor , pharmacology , chemistry , oxidative stress , biochemistry , biology , programmed cell death , apoptosis , receptor
J. Neurochem. (2011) 116 , 1057–1065. Abstract Ginkgo biloba extract (EGb761) has been shown to be neuroprotective; however, the mechanism by which EGb761 mediates neuroprotection remains unclear. We hypothesized that the neuroprotective effect of EGb761 is mediated by inhibition of cytosolic phospholipase A 2 (cPLA 2 ), an enzyme that is known to play a key role in mediating secondary pathogenesis after acute spinal cord injury (SCI). To determine whether EGb761 neuroprotection involves the cPLA 2 pathway, we first investigated the effect of glutamate and hydrogen peroxide on cPLA 2 activation. Results showed that both insults induced an increase in the expression of phosphorylated cPLA 2 (p‐cPLA 2 ), a marker of cPLA 2 activation, and neuronal death in vitro . Such effects were significantly reversed by EGb761 administration. Additionally, EGb761 significantly decreased prostaglandin E 2 (PGE 2 ) release, a downstream metabolite of cPLA 2 . Moreover, inhibition of cPLA 2 activity with arachidonyl trifluromethyl ketone improved neuroprotection against glutamate and hydrogen peroxide‐induced neuronal death, and reversed Bcl‐2/Bax ratio; notably, EGb761 produced greater effects than arachidonyl trifluromethyl ketone. Finally, we showed that the extracellular signal‐regulated kinase 1/2 signaling pathway is involved in EGb761’s modulation of cPLA 2 phosphorylation. These results collectively suggest that the protective effect of EGb761 is mediated, at least in part, through inhibition of cPLA 2 activation, and that the extracellular signal‐regulated kinase 1/2 signaling pathway may play an important role in mediating the EGb761’s effect.