Rapid Activation Of MAPKs By Glucocorticoids In Primary Cultured Rat Hippocampal Cells

In the present study we examined the effect of glucocorticoids on MAPKs of primary cultured hippocampal cells, which represented an extension of previous works in our laboratory studying the action of GC on MAPKs in PC12 cells. The study consisted of two parts.The first parts studied the time course and response strength of MAPKs activation by GC, as well as the actions of distinct blockers of receptors and signal transduction. The results showed that:1. B (10-9M) can activate MAPKs after 5min stimulation2. The activated p44/42 decreased to basal level rapidly while the phosphor-p38 and JNK sustained at high level until 4hr.3. B-BSA can mimic the actions of B4. The pathway leading to GC' s activation of MAPKs was via G-protein-PKC-MAPKs.5. PKA, receptor tyrosine kinase(TRK) and classical nuclear receptor of GC were not involved in the GC' s activation of MAPKsThe second part studied the nuclear translocation of GC activated MAPKs, mainly p38 and JNK , with laser confocal microscopy. The results showed that :1. The p38 and JNK tanslocated into nucleus at 30min after 15min of B stimulation2. B-BSA can mimic the effect of B and caused a translocation which could be observed at 1hr after 15min stimulation of B-BSA.Since many of the kinases studied are involved in the plasticity of hippocampal cells as well as learning and memory in hippocampus , and JNK and p38 are involved in the process of cell death or apoptosis in hippocampal cells, it is suggested that the MAPKs activation by GC' s nongenomic action maybe in some extent in relevance to neuronal plasticity and /or apoptosis in hippocampusIn view of the fact that GC activated MAPKs translocated into the cell nucleus , and maintained in a sustained high level for a long duration, we propose that a genomic consequence could be evoked by this GC activation of MAPKs.