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Phospholipases A2 in Ischemic and Toxic Brain Injury

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Abstract

Phospholipases A2 (PLA2s) regulate hydrolysis of fatty acids, including arachidonic acid, from the sn-2 position of phospholipid membranes. PLA2 activity has been implicated in neurotoxicity and neurodegenerative processes secondary to ischemia and reperfusion and other oxidative stresses. The PLA2s constitute a superfamily whose members have diverse functions and patterns of expression. A large number of PLA2s have been identified within the central nervous systems of rodents and humans. We postulated that group IV large molecular weight, cytosolic phospholipase A2 (cPLA2) has a unique role in neurotoxicity associated with ischemic or toxin stress. We created mice deficient in cPLA2 and tested this hypothesis in two injury models, ischemia/reperfusion and MPTP neurotoxicity. In each model cPLA2 deficient mice are protected against neuronal injury when compared to their wild type littermate controls. These experiments support the hypothesis that cPLA2 is an important mediator of ischemic and oxidative injuries in the brain.

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Authors and Affiliations

  1. Anesthesia and Critical Care and Medical Services, Massachusetts General Hospital, Charlestown, 02129

    Adam Sapirstein & Joseph V. Bonventre

  2. Departments of Anesthesiology and Medicine, Harvard Medical School, Boston, MA, 02114

    Adam Sapirstein & Joseph V. Bonventre

  3. Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Boston and Cambridge, MA

    Adam Sapirstein

  4. Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Boston and Cambridge, MA

    Joseph V. Bonventre

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  1. Adam Sapirstein
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  2. Joseph V. Bonventre
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Sapirstein, A., Bonventre, J.V. Phospholipases A2 in Ischemic and Toxic Brain Injury. Neurochem Res 25, 745–753 (2000). https://doi.org/10.1023/A:1007583708713

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