Inhibiting EZH2 rescued bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia in mice
Purpose In the present work, we intended to explore the function of enhancer of zeste homolog 2 (EZH2) in modulated anesthetic reagent bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia (DRG). Methods Murine DRG explant was treated with 5 mM bupivacaine in vitro to induce neur...
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Veröffentlicht in: | Journal of anesthesia 2018-08, Vol.32 (4), p.524-530 |
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Sprache: | eng |
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Zusammenfassung: | Purpose
In the present work, we intended to explore the function of enhancer of zeste homolog 2 (EZH2) in modulated anesthetic reagent bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia (DRG).
Methods
Murine DRG explant was treated with 5 mM bupivacaine in vitro to induce neuronal apoptosis, which was examined by a TUNEL assay. Protein and mRNA expressions of EZH2 in bupivacaine-treated DRG were examined by western blot and qRT-PCR assays. EZH2 was downregulated by siRNA in bupivacaine-treated DRG. Its functional role in protecting bupivacaine-induced neuronal apoptosis was examined. In addition, apoptotic protein caspase-9 and EZH2-associated signaling pathway, and tropomyosin receptor kinase C (TrkC) were further investigated, by western blot assay, in EZH2-downregulated and bupivacaine-injured DRG.
Results
In vitro treatment of bupivacaine-induced DRG neuronal apoptosis, and upregulated EZH2 at both protein and mRNA levels. SiRNA transfection successfully downregulated EZH2, as confirmed by western blot and qRT-PCR assays. Examination of TUNEL assay showed that EZH2 downregulation rescued bupivacaine-induced DRG neuronal apoptosis. Moreover, in bupivacaine-injured DRG, EZH2 downregulation reduced caspase-9, whereas upregulated TrkC and phosphorylated-TrkC (p-TrkC).
Conclusion
EZH2 is upregulated, whereas inhibiting EZH2 exerted rescuing effect in anesthetics (bupivacaine)-induced spinal cord DRG. The possible downstream target of EZH2 inhibition may interact with caspase and TrkC signaling pathways. |
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ISSN: | 0913-8668 1438-8359 |
DOI: | 10.1007/s00540-018-2506-8 |