Phospholipases A(2) in ischemic and toxic brain injury

Phospholipases A(2) (PLA(2)s) regulate hydrolysis of fatty acids, including arachidonic acid, from the sn-2 position of phospholipid membranes. PLA(2) activity has been implicated in neurotoxicity and neurodegenerative proces ses secondary to ischemia and reperfusion and other oxidative stresses. The PLA(2)s constitute a superfamily whose members have diverse functions and patterns of expression. A large number of PLA(2)s have been identified with in the central nervous systems of rodents and humans. We postulated that gr oup IV large molecular weight, cytosolic phospholipase A(2) (cPLA(2)) has a unique role in neurotoxicity associated with ischemic or toxin stress. We created mice deficient in cPLA(2) and tested this hypothesis in two injury models, ischemia/reperfusion and MPTP neurotoxicity. In each model cPLA(2) deficient mice are protected against neuronal injury when compared to their wild type littermate controls. These experiments support the hypothesis th at cPLA(2) is an important mediator of ischemic and oxidative injuries in t he brain.