Dexmedetomidine suppresses bupivacaine-induced parthanatos in human SH-SY5Y cells via the miR-7-5p/PARP1 axis-mediated ROS.

This study aims to explore the regulatory mechanisms of dexmedetomidine in parthanatos. MTT assay was applied to reveal cell viability; JC-1 staining assay was utilized to reveal mitochondrial membrane potential. Reactive oxygen species (ROS) probe, DCFH-DA, was used to detect intracellular ROS production. Luciferase activity assay was applied to measure the binding between miR-7-5p and PARP1. We first identified that bupivacaine inhibited the viability and induced the parthanatos of human neuroblastoma SH-SY5Y cells. In addition, dexmedetomidine, a potent α2-adrenoceptor agonist, reversed the regulatory effect of bupivacaine on parthanatos of SH-SY5Y. More importantly, dexmedetomidine counteracted bupivacaine-induced changes of mitochondrial membrane potential and ROS production in SH-SY5Y cells. Hyper-activation of PARP1 plays a vital role in parthanatos. Further exploration of our study identified that bupivacaine triggered overexpression of PARP1 in SH-SY5Y cells. Bioinformatics analysis revealed that miR-7-5p targeted the 3' untranslated region (3' UTR) of PARP1 to inhibit PARP1 expression. In addition, dexmedetomidine recovered the suppressive effects of bupivacaine on miR-7-5p expression. Dexmedetomidine suppressed bupivacaine-induced parthanatos in SH-SY5Y cells via the miR-7-5p/PARP1 axis, which may shed a new insight into parthanatos-dependent neuronal injury.