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Article: Mechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress

TitleMechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress
Authors
Keywordsreactive oxygen species
manganese superoxide dismutase
bupivacaine
oxidative stress
apoptotic injury
Issue Date2020
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactaging.com
Citation
Aging, 2020, v. 12 n. 13, p. 13463-13476 How to Cite?
AbstractManganese superoxide dismutase (SOD2) is a key enzyme to scavenge free radical superoxide in the mitochondrion. SOD2 deficiency leads to oxidative injury in cells. Bupivacaine, a local anesthetic commonly used in clinic, could induce neurotoxic injury via oxidative stress. The role and the mechanism of SOD2 regulation in bupivacaine-induced oxidative stress remains unclear. Here, bupivacaine was used to treat Sprague-Dawley rats with intrathecal injection and culture human neuroblastoma cells for developing vivo injury model and vitro injury model. The results showed that bupivacaine caused the over-production of mitochondrial reactive oxygen species (mtROS), the activation of C-Jun N-terminal kinase (JNK), and the elevation of SOD2 transcription. Decrease of mtROS with N-acetyl-L-cysteine attenuated the activation of JNK and the increase of SOD2 transcription. Inhibition of JNK signaling with a small interfering RNA (siRNA) or with sp600125 down-regulated the increase of SOD2 transcription. SOD2 gene knock-down exacerbated bupivacaine-induced mtROS generation and neurotoxic injury but had no effect on JNK phosphorylation. Mito-TEMPO (a mitochondria-targeted antioxidant) could protect neuron against bupivacaine-induced toxic injury. Collectively, our results confirm that mtROS stimulates the transcription of SOD2 via activating JNK signaling in bupivacaine-induced oxidative stress. Enhancing antioxidant ability of SOD2 might be crucial in combating bupivacaine-induced neurotoxic injury.
Persistent Identifierhttp://hdl.handle.net/10722/293252
ISSN
2020 Impact Factor: 5.682
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Zhongjie-
dc.contributor.authorXu, S-
dc.contributor.authorJi, Z-
dc.contributor.authorXu, H-
dc.contributor.authorZhao, W-
dc.contributor.authorXia, Z-
dc.contributor.authorXu, R-
dc.date.accessioned2020-11-23T08:14:03Z-
dc.date.available2020-11-23T08:14:03Z-
dc.date.issued2020-
dc.identifier.citationAging, 2020, v. 12 n. 13, p. 13463-13476-
dc.identifier.issn1945-4589-
dc.identifier.urihttp://hdl.handle.net/10722/293252-
dc.description.abstractManganese superoxide dismutase (SOD2) is a key enzyme to scavenge free radical superoxide in the mitochondrion. SOD2 deficiency leads to oxidative injury in cells. Bupivacaine, a local anesthetic commonly used in clinic, could induce neurotoxic injury via oxidative stress. The role and the mechanism of SOD2 regulation in bupivacaine-induced oxidative stress remains unclear. Here, bupivacaine was used to treat Sprague-Dawley rats with intrathecal injection and culture human neuroblastoma cells for developing vivo injury model and vitro injury model. The results showed that bupivacaine caused the over-production of mitochondrial reactive oxygen species (mtROS), the activation of C-Jun N-terminal kinase (JNK), and the elevation of SOD2 transcription. Decrease of mtROS with N-acetyl-L-cysteine attenuated the activation of JNK and the increase of SOD2 transcription. Inhibition of JNK signaling with a small interfering RNA (siRNA) or with sp600125 down-regulated the increase of SOD2 transcription. SOD2 gene knock-down exacerbated bupivacaine-induced mtROS generation and neurotoxic injury but had no effect on JNK phosphorylation. Mito-TEMPO (a mitochondria-targeted antioxidant) could protect neuron against bupivacaine-induced toxic injury. Collectively, our results confirm that mtROS stimulates the transcription of SOD2 via activating JNK signaling in bupivacaine-induced oxidative stress. Enhancing antioxidant ability of SOD2 might be crucial in combating bupivacaine-induced neurotoxic injury.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactaging.com-
dc.relation.ispartofAging-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectreactive oxygen species-
dc.subjectmanganese superoxide dismutase-
dc.subjectbupivacaine-
dc.subjectoxidative stress-
dc.subjectapoptotic injury-
dc.titleMechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress-
dc.typeArticle-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/aging.103447-
dc.identifier.pmid32658869-
dc.identifier.pmcidPMC7377901-
dc.identifier.scopuseid_2-s2.0-85088495645-
dc.identifier.hkuros319752-
dc.identifier.volume12-
dc.identifier.issue13-
dc.identifier.spage13463-
dc.identifier.epage13476-
dc.identifier.isiWOS:000549883400005-
dc.publisher.placeUnited States-
dc.identifier.issnl1945-4589-

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