The mechanisms of enhanced acidosis on ischemic neuronal damage

据报道，酸化能够激活蛋白质磷酸化、蛋白质合成和即刻早期基因转录。我们的目的是通过注射葡萄糖(高血糖，HG)或添加二氧化碳(高二氧化碳，HC)，来研究全脑缺血时蛋白激酶C亚细胞内再分布的变化。在严重酸中毒的缺血条件下，PKC由胞浆部分向颗粒部分的移位增加。该酶的过度激活(加强的移位)似乎对缺血后的神经元存活有害(Katsura等人)。脑部研究1999)。在酸中毒加重的组中，PKC易位显著增加。这些结果提出了一个问题，即酸中毒的加剧是否影响了脂代谢，特别是游离脂肪酸(FFAs)和二酰甘油酯(DAGs)的释放。选择顶叶皮质是因为HG和HC均显著加重缺血损伤；此外，我们还知道缺血过程中pH值的变化。与我们的预期相反，叠加性酸中毒动物的FFA和DAG含量较少。因此，当PKC易位显著增加时，酸中毒加重的动物在10分钟时DAG水平显著降低。其原因仍有待研究，然而，细胞内钙离子大量内流和各种游离脂肪酸的释放可能会降低DAGs对PKC转位的必要性和依赖性(论文正在准备中)。

Acidification is reported to be able to activate protein phosphorylation, protein synthesis and immediate-early-gene transcription. Our aim is to study the changes in subcellular redistributions of protein kinases C during complete ischemia, changing intraischemic acidotic levels by either injecting glucose (Hyperglycemic, HG) or adding CO2 (Hypercapnic, HC). The translocation of PKC from the cytosolic fraction to particulate fraction was enhanced under ischemia with severe acidosis. Overactivation (the enhanced traslocation) of the enzyme seems to be harmful to the neuronal survival after ischemia (Katsura et al. Brain Research 1999).The PKC translocation was significantly increased in the goups with enhanced acidosis. These results raise questions whether the enhanced acidosis affects the lipid metabloism, especially the release of free fatty acids (FFAs) and diacylglycerides (DAGs). The parietal cortex was chosen since the ischemic damage was significantly aggravated by both HG and HC ; besides, we know the change of pH during ischemia. Countrary to our expectations, the FFA and DAG contents were less in the animals with superimposed acidosis. Thus, animals with enhanced acidosis showed significantly decreased levels of DAGs at 10 min when the PKC translocation is significantly enhanced. The reasons are still to be studied, however, the massive influx of calcium upon cellular deporalization and liberation of various FFAs may decrease the necessity and dependence of DAGs for PKC translocation (paper in preparation).