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Article: Mechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress
Title | Mechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress |
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Authors | |
Keywords | reactive oxygen species manganese superoxide dismutase bupivacaine oxidative stress apoptotic injury |
Issue Date | 2020 |
Publisher | Impact 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? |
Abstract | Manganese 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 Identifier | http://hdl.handle.net/10722/293252 |
ISSN | 2023 Impact Factor: 3.9 2023 SCImago Journal Rankings: 1.180 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Liu, Zhongjie | - |
dc.contributor.author | Xu, S | - |
dc.contributor.author | Ji, Z | - |
dc.contributor.author | Xu, H | - |
dc.contributor.author | Zhao, W | - |
dc.contributor.author | Xia, Z | - |
dc.contributor.author | Xu, R | - |
dc.date.accessioned | 2020-11-23T08:14:03Z | - |
dc.date.available | 2020-11-23T08:14:03Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Aging, 2020, v. 12 n. 13, p. 13463-13476 | - |
dc.identifier.issn | 1945-4589 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293252 | - |
dc.description.abstract | Manganese 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.language | eng | - |
dc.publisher | Impact Journals LLC. The Journal's web site is located at http://www.impactaging.com | - |
dc.relation.ispartof | Aging | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | reactive oxygen species | - |
dc.subject | manganese superoxide dismutase | - |
dc.subject | bupivacaine | - |
dc.subject | oxidative stress | - |
dc.subject | apoptotic injury | - |
dc.title | Mechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress | - |
dc.type | Article | - |
dc.identifier.email | Xia, Z: zyxia@hkucc.hku.hk | - |
dc.identifier.authority | Xia, Z=rp00532 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.18632/aging.103447 | - |
dc.identifier.pmid | 32658869 | - |
dc.identifier.pmcid | PMC7377901 | - |
dc.identifier.scopus | eid_2-s2.0-85088495645 | - |
dc.identifier.hkuros | 319752 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 13 | - |
dc.identifier.spage | 13463 | - |
dc.identifier.epage | 13476 | - |
dc.identifier.isi | WOS:000549883400005 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 1945-4589 | - |