Ropivacaine Induce G0 / G1 Phase Cell Cycle Arrest and Apoptosis of PC12 Cells Via Inhibiting Mitochondrial STAT3 Translocation

Abstract

Signal transducer and activator of transcription 3 (STAT3) has been shown to have neuroprotective effects via the non-canonical activation and mitochondrial translocation, but its effect on ropivacaine induced neurotoxicity is unclear. Our previous studies have revealed that apoptosis was an important mechanism of ropivacaine induced neurotoxicity, so this study is to explore the relationship between STAT3 with ropivacaine induced apoptosis. Our results showed that ropivacaine decreased PC12 cell viability, arrested the cells in the G0 / G1 phase, induced cell apoptosis and oxidative stress, and damaged mitochondrial functions. In addition, the serine727 (Ser727) phosphate activation of STAT3 was inhibited by ropivacaine. Ropivacaine decreased the p-STAT3 (Ser727) expression in the mitochondria, and increased p-STAT3 (Ser727) expression in the cytoplasm, so that it inhibited mitochondrial STAT3 translocation. To explore the potential connection between STAT3 with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and results showed that ropivacaine could bind to STAT3. Furthermore, the apoptosis of the spinal cord was increased and the p-STAT3 (Ser727) expression in the spinal cord was reduced after ropivacaine treatment. our findings illustrated that ropivacaine induced neurotoxicity by increasing the apoptotic levels, the activation and mitochondrial translocation of STAT3 were inhibited by ropivacaine. There may be an internal connection between these phenomena.