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Journal of Anesthesia

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01-08-2018 | Original Article

Inhibiting EZH2 rescued bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia in mice

Authors: Jinwei Zheng, Junping Chen, Guorong Wu, Chaoshuang Wu, Ruichun Wang, Wei Wang

Published in: Journal of Anesthesia | Issue 4/2018

Abstract

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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Title: Inhibiting EZH2 rescued bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia in mice
Authors: Jinwei Zheng
Junping Chen
Guorong Wu
Chaoshuang Wu
Ruichun Wang
Wei Wang
Publication date: 01-08-2018
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 4/2018
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-018-2506-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Inhibiting EZH2 rescued bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia in mice

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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