Role of secretory phospholipase A2 in CNS inflammation

Implications in traumatic spinal cord injury

W. Lee Titsworth, Naikui Liu, Xiao-Ming Xu

Research output: Contribution to journalArticle

32 Citations (Scopus)

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

Fingerprint

Secretory Phospholipase A2
Spinal Cord Injuries
Central Nervous System
Inflammation
Nervous System Trauma
Eicosanoids
Platelet Activating Factor
Wounds and Injuries
Nonesterified Fatty Acids
Brain Injuries
Phospholipids
Spinal Cord
Lysophospholipids
Glycerophospholipids
Excitatory Amino Acids
Membranes
Multiple Trauma
Poisons
Isoenzymes
Free Radicals

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

Cite this

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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.",
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