Ischemia-induced changes in cerebral mitochondrial free fatty acids, phospholipids, and respiration in the rat.
Changes in the free fatty acid pool size and fatty acyl chain composition of mitochondrial membrane phospholipids and their relation to disruption of mitochondrial function were examined in rat brains after 30 min of cerebral ischemia (Pulsinelli-Brierley model) and 60 min of normoxic reoxygenation. During ischemia, significant hydrolysis of polyunsaturated molecular species from diacyl phosphatidylcholine, particularly fatty acyl 20:4 (arachidonic acid; 20% decrease) and 22:6 (docosahexaenoic acid; 15% decrease), was observed. Thirty minutes of ischemia caused a 16% loss of 18:2 (linoleic acid) from phosphatidylethanolamine. Recirculation for 60 min did not return the polyunsaturated fatty acid content of phospholipids to normal. Total content of free fatty acids increased during ischemia, particularly 18:2 and 22:6, which exhibited the most dramatic rise. The free fatty acid pool size continued to increase during 60 min of recirculation. The respiratory control ratio decreased significantly during 30 min of ischemia with no apparent recovery following 60 min of reoxygenation. The degree of free radical-mediated lipid peroxidation in mitochondria was significantly increased during ischemia and reperfusion. It was concluded that (a) 30 min of cerebral ischemia caused differential degradation in each of the phospholipid classes and preferential hydrolysis of the polyunsaturated molecular species and (b) 60 min of normoxic reperfusion failed to promote reacylation of the mitochondrial phospholipids and restoration of normal respiration.
Sun
D
D
Department of Neurosurgery, University of Wisconsin Medical School, Madison 53706.
Gilboe
D D
DD
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010743:Phospholipids / Q000378:metabolism*; D016548:Prosencephalon; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D008565:Membrane Proteins; D010743:Phospholipids; D008315:Malondialdehyde