Phospholipase A2 and its Molecular Mechanism after Spinal Cord Injury

Abstract

Phospholipases A(2) (PLA(2)s) are a diverse family 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 which have been implicated in pathological states of numerous acute and chronic neurological disorders. To date, more than 27 isoforms of PLA(2) have been found in the mammalian system which can be classified into four major categories: secretory PLA(2), cytosolic PLA(2), Ca(2+)-independent PLA(2), and platelet-activating factor acetylhydrolases. Multiple isoforms of PLA(2) are found in the mammalian spinal cord. Under physiological conditions, PLA(2)s are involved in diverse cellular responses, including phospholipid digestion and metabolism, host defense, and signal transduction. However, under pathological situations, increased PLA(2) activity, excessive production of free fatty acids and their metabolites may lead to the loss of membrane integrity, inflammation, oxidative stress, and subsequent neuronal injury. There is emerging evidence that PLA(2) plays a key role in the secondary injury process after traumatic spinal cord injury. This review outlines the current knowledge of the PLA(2) in the spinal cord with an emphasis being placed on the possible roles of PLA(2) in mediating the secondary SCI.