Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death

Zhen Zhao, Naikui Liu, Jingya Huang, Pei Hua Lu, Xiao-Ming Xu

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 A2 (cPLA2), 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 cPLA2 pathway, we first investigated the effect of glutamate and hydrogen peroxide on cPLA2 activation. Results showed that both insults induced an increase in the expression of phosphorylated cPLA2 (p-cPLA2), a marker of cPLA 2 activation, and neuronal death in vitro. Such effects were significantly reversed by EGb761 administration. Additionally, EGb761 significantly decreased prostaglandin E2 (PGE2) release, a downstream metabolite of cPLA2. 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 cPLA2 phosphorylation. These results collectively suggest that the protective effect of EGb761 is mediated, at least in part, through inhibition of cPLA2 activation, and that the extracellular signal-regulated kinase 1/2 signaling pathway may play an important role in mediating the EGb761's effect.

Original languageEnglish
Pages (from-to)1057-1065
Number of pages9
JournalJournal of Neurochemistry
Volume116
Issue number6
DOIs
StatePublished - Mar 2011

Fingerprint

Cytosolic Phospholipases A2
Ginkgo biloba
Oxidative stress
Cell death
Neurons
Glutamic Acid
Spinal Cord
Oxidative Stress
Cell Death
Chemical activation
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Ketones
Hydrogen Peroxide
Ginkgo biloba extract 761
Phosphorylation
Neuroprotective Agents
Metabolites
Spinal Cord Injuries
Dinoprostone

Keywords

  • cytosolic phospholipase A
  • EGb761
  • excitotoxicity
  • neuronal death
  • oxidative injury
  • spinal cord neurons

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death. / Zhao, Zhen; Liu, Naikui; Huang, Jingya; Lu, Pei Hua; Xu, Xiao-Ming.

In: Journal of Neurochemistry, Vol. 116, No. 6, 03.2011, p. 1057-1065.

Research output: Contribution to journalArticle

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