Role of NFAT4-Trim17 axis mediates the neuronal apoptosis after subarachnoid hemorrhage

Abstract

Abstract Background: Although accumulating evidence indicates that Trim17 is implicated in the pathophysiology of neuronal apoptosis, the regulation mechanism on pro-apoptotic role of Trim17 after subarachnoid hemorrhage (SAH) has not been well identified so far. Methods: Trim17 siRNA was administered to explore the detrimental role of Trim17 in mediating neuronal apoptosis in vivo and in vitro after experimental SAH. The nuclear factor of activated T cells (NFAT) signaling, involving in the underlying regulation mechanism on Trim17, was further explored. Results: Trim17 mainly located in the neurons and presented an obvious elevated expression in vivo and in vitro after SAH. Trim17 siRNA administration could significantly ameliorate neuronal apoptosis after SAH. Moreover, inhibition the nuclear translocation of NFAT4 could effectively abolishthe pro-apoptotic activity of Trim17/Bax pathway, accompanied by ameliorated neuronal apoptosis and improved neurological function. Conclusions: The elevation of Trim17 is sufficient for triggering the intrinsic apoptotic effect after SAH, and this pro-apoptotic activity could be mediated by the initiated of the nuclear translocation of NFAT4. Pharmacological targeting of NFAT4/Trim17 pathway can be explored for SAH therapy.