Regulation of FFA by the acyltransferase pathway in focal cerebral ischemia-reperfusion.
Cerebral insult is associated with a rapid increase in free fatty acids (FFA) and arachidonic acid release has been linked to the increase in eicosanoid biosynthesis. In transient focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion, there is an inverse relationship between the increase in FFA and the decrease in ATP, both during the ischemia period and at later time periods after reperfusion. In this study, the focal cerebral ischemia model was used to examine incorporation of [14C]arachidonic acid into the glycerolipids in rat MCA cortex at different reperfusion times after a 60 min ischemia. The label was injected intracerebrally into left and right MCA cortex 1 hr prior to decapitation. Labeled arachidonic acid was incorporated into phosphatidylcholine, phosphatidylethanolamine and neutral glycerides. With increasing time (4-16 hr) after a 60 min ischemia, an inhibition of labeled arachidonate uptake could be found in the right ischemic MCA cortex, whereas the distribution of radioactivity among the major phospholipids was not altered. When compared to labeled PC, there was a 3-4 fold increase in incorporation of label into phosphatidic acid and triacylglycerols (TG) in the right MCA cortex, suggesting of an increase in de novo biosynthesis of TG. In an in vitro assay system, synaptosomal membranes isolated from MCA cortex 8 and 16 hr after a 60 min ischemia showed a significant decrease in arachidonoyl transfer to lysophospholipids, due mainly to a decrease in lysophospholipid:acylCoA acyltransferase activity. Assay of phospholipase A2 activity with both syaptosomes and cytosol, however, did not show differences between left and right MCA cortex or with time after reperfusion. These results suggest that besides ATP availability, the decrease in acyltransferase activity may also contribute to the increase in FFA in cerebral ischemia-reperfusion.
Zhang
J P
JP
Biochemistry Department, University of Missouri, Columbia 65212, USA.
Sun
G Y
GY
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism; D000217:Acyltransferases / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D005989:Glycerides / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology*; D050356:Lipid Metabolism; D008297:Male; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*; D013347:Subcellular Fractions / Q000201:enzymology
D005230:Fatty Acids, Nonesterified; D005989:Glycerides; D016718:Arachidonic Acid; D000217:Acyltransferases; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2