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 prod...
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Veröffentlicht in: | Naunyn-Schmiedeberg's archives of pharmacology 2021-04, Vol.394 (4), p.783-796 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0028-1298 1432-1912 |
DOI: | 10.1007/s00210-020-01971-6 |