The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids.
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.
Green
Joshua T
JT
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Orr
Sarah K
SK
Bazinet
Richard P
RP
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D008322:Mammals; D054467:Phospholipases A2 / Q000097:blood / Q000145:classification / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology
D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D054467:Phospholipases A2; D002118:Calcium