| Co-Investigator(Kenkyū-buntansha) |
MIZUGAKI Michinao Tohoku University Hospital, 医学部付属病院, 教授 (60004595)
ENDO Masao Yamagata University School of Medicine, 医学部, 教授 (40004668)
MOTOMIYA Masakichi Institute of Tuberculosis and Cancer, Tohoku University, 抗酸菌病研究所, 教授 (20006092)
片倉 隆一 東北大学, 医学部・脳神経外科, 助手 (70152676)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1987: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Research Abstract |
Polyphosphoinositides: phosphatidylinositol (PI), phosphatidylinositol 4, phosphate (PIP), phosphatidylinositol - 4, 5, bisphosphate (PIP_2) are suggested to be closely linked to cellular signal transduction mechanism. They are importnat in considering the mechanism of the release of free fatty acids (FFAs). However, the exact mechanism of liberation of FFAs, in relation to phospholipase C (PIC) and phospholipase A (PLA) activities during ischemia has not yet been elucidated. The status of the membrane lipid metabolism after recirculation following ischemia is still unclear. We have quantified polyphosphoinositide, 1,2 - diglyceride (DG), lysophospholipid, FFAs, and key energy metabolites in transient global cerebral ischemia of rats. The fatty acid composition of individual lipids were studied also. PIP_2 and PIP decreased rapidly during 5 min of ischemia and, thereafter gradually. While DG increased almost at the same rate. There was a transient increase of stearic acid and arachidon
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ic acid in DG. PIP_2 and PIP recovered completely after recirculation following both 5 and 30 min of ischemia. DG returned to the preischemic level at 30 min of recirculation. Lyso-phosphatidylcholine increased two-hold during 5 min of ischemia followed by a steady decline in continuous ischemia. The level of lysophosphatidylcholine returned to the control values after recir-culation. The relative percentage of saturated fatty acid of lysophosphatidylcholine increased during ischemia, and returned to the control value after recirculation. Of the FFAs accumulated during ischemia, stearic acid and arachidonic acid rapidly increased in the earlier stage of ischemia within 5 min followed by an increase of other FFAs. All of the individual FFAs decreased after recirculation. Unsaturated FFAs decreased more rapidly than saturated FFAs and returned to the preischemic value at 60 min of recirculation. Polyphosphoinositide metabolism that was affected by ischemia was reversible on recirculation. ATP and CTP decreased markedly after the onset of ischemia and reached nadir. They did not recover to the preischemic value at 60 min of recirculation. These results showed that an increase of FFAs during 5 min of ischemia may be derived from acyl groups of DG by degradation of PIP_2 and PIP, and hydrolysis of phospholipid by PLA@>D22@>D2. In the later period of ischemia, FFAs accumulated mainly due to the combined action of PLA_2 and lysophospholipase. After recirculation, FFAs that were accumulated during ischemia are used for the resynthesis of polyphosphoinositides (de novo) and reacylation of phospholipids. We also examined the inositol phospholipid metabolism in the brain slice and the synaptosome. But we could not get reliable data. Further examinations will be needed. Less
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