Submitted on October 15, 2007
Revised on December 20, 2007
Accepted on February 5, 2008
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. Bazinet
Nutritional Sciences, University of Toronto, Toronto, ON M5S 3E2
Corresponding Author: richard.bazinet{at}utoronto.ca
Brain phospholipids are highly enriched in docosahexaenoic acid (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 (i)PLA2. 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.