Inositol phospholipid metabolism in cerebral ischemia

聚磷酸肌醇：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）与细胞信号转导机制密切相关。它们在考虑游离脂肪酸（FFA）释放的机制中是重要的。然而，在缺血过程中游离脂肪酸释放的确切机制，与磷脂酶C（PIC）和磷脂酶A（PLA）的活动尚未阐明。缺血后再循环后膜脂代谢的状态仍不清楚。我们已经定量的多磷酸肌醇，1，2-甘油二酯（DG），溶血磷脂，游离脂肪酸，和关键的能量代谢产物在短暂的全脑缺血大鼠。还研究了单个脂质的脂肪酸组成。PIP_2和PIP在缺血5 min内迅速下降，以后逐渐下降。而DG几乎以相同的速度增加。硬脂酸和花生四烯酸有短暂的增加 ...更多信息 DG中的酸。缺血5 min和30 min再灌注后，PIP_2和PIP均完全恢复。DG在再循环30 min时恢复到缺血前水平。溶血磷脂酰胆碱增加两个举行在5分钟的缺血，随后在连续缺血稳定下降。再循环后溶血磷脂酰胆碱水平恢复至对照值。溶血磷脂酰胆碱中饱和脂肪酸的相对百分比在缺血时增加，再灌注后恢复到对照值。在缺血过程中积累的游离脂肪酸中，硬脂酸和花生四烯酸在缺血早期5分钟内迅速增加，随后其他游离脂肪酸增加。再循环后，所有个体FFA均降低。不饱和游离脂肪酸下降速度比饱和游离脂肪酸，并返回到缺血前的值在60分钟的再循环。受缺血影响的多磷酸肌醇代谢在再循环时是可逆的。ATP和CTP在缺血后明显下降并达最低点。在再循环60分钟时，它们没有恢复到缺血前的值。结果表明，缺血5 min内游离脂肪酸的增加可能是由于PIP_2和PIP降解DG的酰基以及PLA@>D22@>D2水解磷脂所致。缺血后期，FFAs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用于再合成聚磷酸肌醇（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。少

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