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Journal of Lipid Research, Vol. 44, 109-117, January 2003
Copyright © 2003 by Lipid Research, Inc.

Brain lipid metabolism in the cPLA₂ knockout mouse

Thad A. Rosenberger^1,*, Nelly E. Villacreses^*, Miguel A. Contreras^*, Joseph V. Bonventre and Stanley I. Rapoport^*

^* Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892
Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129

¹ To whom correspondence should be addressed. e-mail: plsetn{at}mail.nih.gov

We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A₂ (cPLA_2, Type IV, 85 kDa) was knocked out (cPLA₂^-/- mice). Compared with controls, these mice demonstrated altered brain concentrations of several phospholipids, reduced esterified linoleate, arachidonate, and docosahexaenoate in choline glycerophospholipid, and reduced esterified arachidonate in phosphatidylinositol. Unanesthetized cPLA₂^-/- mice had reduced rates of incorporation of unlabeled arachidonate from plasma and from the brain arachidonoyl-CoA pool into ethanolamine glycerophospholipid and choline glycerophospholipid, but elevated rates into phosphatidylinositol. These differences corresponded to altered turnover and metabolic loss of esterified brain arachidonate. These results suggests that cPLA₂ is necessary to maintain normal brain concentrations of phospholipids and of their esterified polyunsaturated fatty acids.

Reduced esterified arachidonate and docosahexaenoate may account for the resistance of the cPLA₂^-/- mouse to middle cerebral artery occlusion, and should influence membrane fluidity, neuroinflammation, signal transduction, and other brain processes.

Abbreviations: AA, arachidonic acid; CerP Cho, sphingomyelin; ChoGpl, choline glycerophospholipid; DHA, docosahexaenoic acid; DG, diacylglycerol; EtnGpl, ethanolamine glycerophospholipid; PAF, platelet activating factor; PLA₂, phospholipases A₂; cPLA₂, cytosolic phospholipase A₂; PlsCho, plasmenylcholine; PtdCho, phosphatidylcholine; PlsEtn, plasmenylethanolamine; PtdEtn, phosphatidylethanolamine; PtdIns, phosphatidylinositol; PtdSer, phosphatidylserine; PUFA, polyunsaturated fatty acid; sPLA₂, secretory phospholipase A₂; TG, triacylglycerol

Supplementary key words arachidonate • docosahexaenoate • phospholipase A₂ • phospholipid • turnover • kinetics

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