Skip to Content
Merck
  • Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury.

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

Annals of neurology (2014-03-14)
Nai-Kui 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
ABSTRACT

The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2 ), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI). 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Prostaglandin E2, synthetic, powder, BioReagent, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Prostaglandin E2, γ-irradiated, powder, BioXtra, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Prostaglandin E2, ≥93% (HPLC), synthetic
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Arachidonyl trifluoromethyl ketone, oil, ≥97% (NMR)
SKU
Pack Size
Availability
Price
Quantity
Dinoprostone, European Pharmacopoeia (EP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, BioUltra, ≥99% (titration)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity