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Inositol phospholipid metabolism in cerebral ischemia

脑缺血时肌醇磷脂代谢

基本信息

批准号：
62480303
负责人：
KATAKURA Ryuichi
金额：
$ 4.35万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

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 … More 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

多磷酸肌醇：磷脂酰肌醇（PI）、磷脂酰肌醇4、磷酸（PIP）、磷脂酰肌醇-4、5、二磷酸（PIP_2）被认为与细胞信号转导机制密切相关。它们对于考虑游离脂肪酸 (FFA) 的释放机制非常重要。然而，缺血期间与磷脂酶 C (PIC) 和磷脂酶 A (PLA) 活性相关的 FFA 释放的确切机制尚未阐明。缺血再循环后膜脂代谢的状态仍不清楚。我们对大鼠短暂性全脑缺血中的多磷酸肌醇、1,2-甘油二酯 (DG)、溶血磷脂、FFA 和关键能量代谢物进行了定量。还研究了各种脂质的脂肪酸组成。 PIP_2 和 PIP 在缺血 5 分钟内迅速下降，此后逐渐下降。而DG几乎以同样的速度增长。 DG 中的硬脂酸和花生四烯酸短暂增加。缺血 5 分钟和 30 分钟后，PIP_2 和 PIP 在再循环后完全恢复。再循环 30 分钟时 DG 恢复至缺血前水平。溶血磷脂酰胆碱在缺血 5 分钟期间增加两次保持，随后在连续缺血中稳定下降。再循环后溶血磷脂酰胆碱水平恢复至对照值。溶血磷脂酰胆碱饱和脂肪酸的相对百分比在缺血期间增加，并在再循环后恢复到对照值。缺血期间积累的FFA中，硬脂酸和花生四烯酸在缺血早期5分钟内迅速增加，随后其他FFA也增加。再循环后所有个体 FFA 均减少。不饱和 FFA 比饱和 FFA 下降得更快，并在再循环 60 分钟时恢复到缺血前值。受缺血影响的多磷酸肌醇代谢在再循环时是可逆的。缺血发生后ATP和CTP显着下降并达到最低点。再循环 60 分钟时，它们没有恢复到缺血前的值。这些结果表明，缺血5分钟期间FFA的增加可能源自DG的酰基通过PIP_2和PIP的降解以及PLA@>D22@>D2对磷脂的水解。缺血后期，FFA的积累主要是由于PLA_2和溶血磷脂酶的共同作用。再循环后，缺血期间积累的 FFA 用于重新合成多磷酸肌醇（从头）和磷脂的再酰化。我们还检查了脑切片和突触体中的肌醇磷脂代谢。但我们无法获得可靠的数据。还需要进一步检查。较少的