Molecular mechanisms of exaggerated acidosis on ischemic neuronal damage

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To explore effects of Immunosuppressant FK506 on signal translduction pathway, we studied changes in subcellular distribution of protein kinase Cγ (PKCγ), CaM kinase II (CaMKII), as well as changes of tyrosine phosphorylation levels after ischemia. FK506 administration significantly decreased translocation of PKCγ and CaMKII at 24 h of recovery in P2 fraction. The levels of tyrosine phosphorylated p160, p140, p100, p90, and p80 in P2 fraction were decreased with FK506 treatment at 24h of recovery. The persistently elevated PKCγ and CaMKII level in P2 fraction which may be related to cell death, are attenuated with FK506 treatment. FK506 may contribute to recover calcium homeostasis in post ischemic phase and promote cell survival.Hyperglycemia and hypercapnia aggravate intra-ischemic acidosis and subsequent brain damage. However, hyperglycemia causes more extensive post-ischemic damage than hypercapnia, particularly in the cingulate cortex. We investigated the changes in the subcellula … More r distribution of PKCγ and CaMKII, as well as changes in protein tyrosine phosphorylation during and following 10 min normoglycemic, hyperglycemic global cerebral ischemia. During reperfusion period, the translocation to cell membranes of PKCγ, but not CaMKII, was prolonged by intra-ischemic hyperglycemia, while it was only marginally affected by hypercapnia. The tyrosine-phosphorylation of proteins in the synaptosomal membranes ; as well as the extracellular signal-regulated kinase (ERK) in the cytosol, markedly increased during reperfusion following hyperglycemic ischemia, but to a lesser degree following hypercapnic ischemia. Our data suggest that PKCγ, tyrosine kinase and ERK systems are involved in the process of ischemic damage in the cigulate cortex, where hyperglycemia may affect these kinases through an additional mechanism other than exaggerated acidosis.I also tried the mechanisms of mitochondrial neuroprotection through Bcl-xL and its derivative, and also tried to explore how to introduce various genes into ischemic brain tissue. Less