Abstract
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.
Highlights
We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A2 was knocked out
We examine brain lipid metabolism in a mouse in which the 85 kDa type IVA cytostolic phospholipases A2 (PLA2) is absent [16,17,18]. cPLA2 is selective for arachidonic acid (AA) over other fatty acids [1] and requires both Ca2ϩ and phosphorylation for full activation [3, 19]
A value for equal to 0.04 indicates that about 4% of arachidonoyl-CoA is derived from plasma, with 96% derived by release from phospholipids [38, 39]
Summary
We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A2 (cPLA2, 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. The female knockout mouse has a reduced reproductive ability, whereas adult males are more resistant to middle cerebral artery occlusion than are con-
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