The mechanisms of enhanced acidosis on ischemic neuronal damage

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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).