CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction

Abstract

Recent studies showed that Ceramide Kinase-Like Protein (CERKL)was expressed in the nerve cells and could regulate autophagy. Sirtuin-1 (SIRT1) is the regulator of the mitophagy, which can be stabilized by CERKL. Furthermore, the study also revealed that the SIRT1 induced mitophagy by activating PINK1/Parkin signaling. Therefore, we speculated that CERKL has potential to activate the SIRT1/PINK1/Parkin pathway to induce mitophagy. In this study, cerebral ischemia reperfusion mouse model was established. CERKL was overexpressed in those mice and human neuroblastoma cells. Tunel staining and flow cytometry were applied for the detection of cell apoptosis. The ratios of LC3Ⅱ to LC3Ⅰ and the expression of LC3Ⅱ in mitochondria were determined by gel electrophoresis. Overexpression of CERKL alleviated the cerebral ischemia reperfusion injury and damage to OGD/R human neuroblastoma cells. Overexpression of CERKL enhanced the expression of LC3 Ⅱ in mitochondria and induced occurrence of mitophagy. Overexpression of CERKL promoted the stability of SIRT1 and facilitated the expression of PINK1 and Parkin in those cells. Knockdown of PINK1 impeded the mitophagy and suppressed the expression of LC3 Ⅱ in mitochondria. It can be concluded that CERKL alleviated the ischemia reperfusion induced nervous system injury through inducing mitophagy in a SIRT1/PINK1/Parkin dependent pathway.