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

Year: 2014
Type: article
Abstract: OBJECTIVE: 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). 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.
DOI: 10.1002/ana.24134
Authors: 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
Institutions: Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, Norton Healthcare, Brigham and Women's Hospital, Harvard University
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $4,700
Funders: Indiana Clinical and Translational Sciences Institute, Indiana State Department of Health, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: Mechanisms of Ischemic Kidney Injury and Repair, G1940434036, G1949062175, Two novel cPLA2 binding proteins and cell death, Role of phospholipase A2 in spinal cord secondary injury, G3405207134, G3581889325, G4238577260, G453062464, Indiana Clinical and Translational Science Institute (UL1), G572954382, G5886875973, G5938045716, Role of Acrolein in Spinal Cord Injury, G6541536589, Two novel cPLA2 binding proteins and cell death, G6954330452, G798517211, Tissue engineering in spinal cord regeneration, G8358840730, G9000003322, G9000081064, G9000309841, G9000315265, Mechanisms of Ischemic Kidney Injury and Repair
OpenAlex ID: W2151407568
FWCI: 5.444
Cites: 61
Cited by: 86
Related to: 10