Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury

Naikui Liu, Ling Xiao Deng, Yi Ping Zhang, Qing Bo Lu, Xiao Fei Wang, Jian Guo Hu, Eddie Oakes, Joseph V. Bonventre, Christopher B. Shields, Xiao-Ming Xu

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Objective The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2), an important isoform of PLA 2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI). Methods A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice. Results SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI. Interpretation cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI.

Original languageEnglish
Pages (from-to)644-658
Number of pages15
JournalAnnals of Neurology
Volume75
Issue number5
DOIs
StatePublished - 2014

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Cytosolic Phospholipases A2
Spinal Cord Injuries
Proteins
Therapeutics
Extracellular Signal-Regulated MAP Kinases
Recovery of Function
Oligodendroglia
Calcimycin
Inbred C57BL Mouse
Arachidonic Acid
Spinal Cord
Protein Isoforms
Cell Death
Thorax
Neurons

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury. / Liu, Naikui; Deng, Ling Xiao; Zhang, Yi Ping; Lu, Qing Bo; Wang, Xiao Fei; Hu, Jian Guo; Oakes, Eddie; Bonventre, Joseph V.; Shields, Christopher B.; Xu, Xiao-Ming.

In: Annals of Neurology, Vol. 75, No. 5, 2014, p. 644-658.

Research output: Contribution to journalArticle

Liu, N, Deng, LX, Zhang, YP, Lu, QB, Wang, XF, Hu, JG, Oakes, E, Bonventre, JV, Shields, CB & Xu, X-M 2014, 'Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury', Annals of Neurology, vol. 75, no. 5, pp. 644-658. https://doi.org/10.1002/ana.24134
Liu, Naikui ; Deng, Ling Xiao ; Zhang, Yi Ping ; Lu, Qing Bo ; Wang, Xiao Fei ; Hu, Jian Guo ; Oakes, Eddie ; Bonventre, Joseph V. ; Shields, Christopher B. ; Xu, Xiao-Ming. / Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury. In: Annals of Neurology. 2014 ; Vol. 75, No. 5. pp. 644-658.
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