Role of secretory phospholipase A2 in CNS inflammation: Implications in traumatic spinal cord injury

W. Lee Titsworth, Nai Kui Liu, Xiao Ming Xu

Research output: Contribution to journalReview article

32 Scopus citations

Abstract

Secretory phospholipases A2 (sPLA2s) are a subfamily of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor (PAF). The hydrolysis of membrane phospholipids by PLA2 is a rate-limiting step for generation of eicosanoids and PAF. To date, more than 10 isozymes of sPLA2 have been found in the mammalian central nervous system (CNS). Under physiological conditions, sPLA2s are involved in diverse cellular responses, including host defense, phospholipid digestion and metabolism. However, under pathological situations, increased sPLA2 activity and excessive production of free fatty acids and their metabolites may lead to inflammation, loss of membrane integrity, oxidative stress, and subsequent tissue injury. Emerging evidence suggests that sPLA2 plays a role in the secondary injury process after traumatic or ischemic injuries in the brain and spinal cord. Importantly, sPLA2 may act as a convergence molecule that mediates multiple key mechanisms involved in the secondary injury since it can be induced by multiple toxic factors such as iflammatory cytokines, free radicals, and excitatory amino acids, and its activation and metabolites can exacerbate the secondary injury. Blocking sPLA2 action may represent a novel and efficient strategy to block multiple injury pathways associated with the CNS secondary injury. This review outlines the current knowledge of sPLA2 in the CNS with emphasis placed on the possible roles of sPLA2 in mediating CNS injuries, particularly the traumatic and ischernic injuries in the brain and spinal cord.

Original languageEnglish (US)
Pages (from-to)254-269
Number of pages16
JournalCNS and Neurological Disorders - Drug Targets
Volume7
Issue number3
DOIs
StatePublished - Jun 1 2008

Keywords

  • And cytokines
  • Excitatory amino acids
  • Inflammation
  • Ischemia
  • Lipid metabolism
  • Phospholipases A
  • Reactive oxygen species
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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