Brain lipid metabolism in the cPLA2 knockout mouse.
We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A(2) (cPLA(2,) Type IV, 85 kDa) was knocked out (cPLA(2)(-/-) 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 cPLA(2)(-/-) 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 cPLA(2) 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 cPLA(2)(-/-) mouse to middle cerebral artery occlusion, and should influence membrane fluidity, neuroinflammation, signal transduction, and other brain processes.
Rosenberger
Thad A
TA
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Villacreses
Nelly E
NE
Contreras
Miguel A
MA
Bonventre
Joseph V
JV
Rapoport
Stanley I
SI
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D017353:Gene Deletion; D054513:Group IV Phospholipases A2; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D010741:Phospholipases A / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014316:Tritium
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; C516390:Pla2g4a protein, mouse; D014316:Tritium; D016718:Arachidonic Acid; D010741:Phospholipases A; D054513:Group IV Phospholipases A2