Suppression of STIM1 in the early stage after global ischemia attenuates the injury of delayed neuronal death by inhibiting store-operated calcium entry-induced apoptosis in rats

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Ca2+ overload is considered to be the most important ion imbalance in the neuronal injury. Store-operated Ca2+ entry has been suggested to be a significant mechanism of excessive Ca2+ influx in many cells. The role of store-operated Ca2+ entry in neuronal ischemic injury has yet to be elucidated. The aim of this study was to assess the role of store-operated calcium channel (SOCC) proteins involved with calcium overload in the induction of delayed neuronal death after global ischemia in rats. A transient RNA interference model of global ischemia in rats was established to determine the role of SOCC-induced Ca2+ overload in delayed neuronal death. We found that STIM1 and ORAI1 expression in the hippocampus increased continuously after global ischemia and peaked on day 4. These data were consistent with an increase in the intracellular calcium concentration. Using Stim1 siRNA to suppress SOCC activity in the early stage of ischemia significantly inhibited STIM1 and ORAI1 expression and decreased the intracellular calcium concentration in neurons. In addition, the neurological function of rats improved after the Stim1 siRNA injection. High expression of STIM1 and ORAI may be the source of excessive calcium influx after ischemic damage. Blocking of this SOCC-induced calcium influx could lead to an improved neuronal survival. These data suggest that calcium influx through SOCC is another nonexcitotoxicity mechanism of ischemic neuronal death.

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