Functional analysis of phospholipid metabolizing enzymes during cell death after ischemia

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In previous study, we demonstrated that diacylglycerol kinase (DGK)z which is distributed at nucleus in normal hippocampal neuron in vivo, is translocated to cytoplasm from nucleus by middle cerebral artery infarction in rat. But it is unclear that the mechanisms of ischemia induced translocation of DGKz and the physiological functions after localization in cytoplasm of DGKz. In this study, we demonstrated that DGKz nuclear export is regulated that calcium influx signaling after ischemia. Moreover, cytoplasmic DGKz is poly-ubiquitinated and degradated in hippocampal neuron in vitro and in vivo. This downregulation causes ER stress induced cell death following expression of cyclin D and cyclin E in neurons after ischema using DGKz deficient mice and siRNA knocdown study in vivo and in vitro. These datas suggest that DGKz is a downregulator of ischemic calcium signaling by inhibiting cyclin expression and cell cycle re-entry of neurons.