Protective Effect Of SGK1 In Rat Hippocampal Neurons Subjected To Ischemia Reperfusion

Objectives:To investigate the protective effect of SGK1 (serum-and glucocorticoid inducible protein kinase 1) in rat hippocampal neurons in vitro and in vivo following ischemia reperfusion (I/R).Methods:Isolated rat hippocampal neurons were subjected to 2 h of oxygen and glucose deprivation (OGD) then returned to normoxic conditions for 10,30 or 60 min. Cell apoptosis and protein expression of SGK1 were analyzed. To examine SGK1 function, we over-expressed SGK1 in rat hippocampal neurons. Finally we examined the involvement of PI3K/Akt/GSK3β signaling by treating the cells (untransfected or transfected with expression vector encoding SGK1) with the PI3K inhibitor LY294002. Findings were confirmed in vivo in a rat model of middle cerebral artery occlusion.Results:I/R caused a time-dependent increase in apoptosis, both in vitro and in vivo. SGK1 protein levels decreased significantly under the same conditions. Overexpression of SGK1 reduced apoptosis following OGD or I/R compared to cells transfected with empty vector and subjected to the same treatment, or sham-operated animals. Addition of LY294002 revealed that the action of SGK1 in suppressing apoptosis was mediated by the PI3K/Akt/GSK3β pathway.Conclusions:SGK1 plays a protective role in ischemia reperfusi on in rat hippocampalneurons, exerting its effects via the PI3K/Akt/GSK3 β pathway.