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Journal of Lipid Research, Vol. 49, 939-944, May 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Review

The emerging role of group VI calcium-independent phospholipase A₂ in releasing docosahexaenoic acid from brain phospholipids

Joshua T. Green, Sarah K. Orr and Richard P. Bazinet¹

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3E2, Canada

Published, JLR Papers in Press, February 5, 2008.

¹ To whom correspondence should be addressed. e-mail: richard.bazinet{at}utoronto.ca

Brain phospholipids are highly enriched in docosahexaenoic acid (DHA; 22:6n-3). Recent advances indicate that 22:6n-3 is released from brain phospholipids via the action of phospholipase A₂ (PLA₂) in response to several stimuli, including neurotransmission, where it then acts as a secondary messenger. Furthermore, it is now known that released 22:6n-3 is a substrate for several oxygenation enzymes whose products are potent signaling molecules. One emerging candidate PLA₂ involved in the release of 22:6n-3 from brain phospholipids is the group VI calcium-independent phospholipase A₂ (iPLA₂). After a brief review of brain 22:6n-3 metabolism, cell culture and rodent studies facilitating the hypothesis that group VI iPLA₂ releases 22:6n-3 from brain phospholipids are discussed. The identification of PLA₂s involved in cleaving 22:6n-3 from brain phospholipids could lead to the development of novel therapeutics for brain disorders in which 22:6n-3 signaling is disordered.

Supplementary key words signaling • cyclooxygenase • lipoxygenase • docosanoid • neuroprotectin • uptake • turnover • kinetics • neuroinflammation • arachidonic acid

Abbreviations: 18:2n-6, linoleic acid; 20:4n-6, arachidonic acid; 22:6n-3, docosahexaenoic acid; cPLA₂, cytosolic phospholipase A₂; iPLA₂, calcium-independent phospholipase A₂; PLA₂, phospholipase A₂; sPLA₂, secretory phospholipase A₂

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