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High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells

Bupivacaine, a typical local anesthetic, induces neurotoxicity via reactive oxygen species regulation of apoptosis. High glucose could enhance bupivacaine-induced neurotoxicity through regulating oxidative stress, but the mechanism of it is not clear. Mitochondrial calcium uniporter (MCU), a key cha...

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Autores principales: Liu, Zhong-Jie, Zhao, Wei, Lei, Hong-Yi, Xu, Hua-Li, Lai, Lu-Ying, Xu, Rui, Xu, Shi-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398017/
https://www.ncbi.nlm.nih.gov/pubmed/30911349
http://dx.doi.org/10.1155/2019/7192798
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author Liu, Zhong-Jie
Zhao, Wei
Lei, Hong-Yi
Xu, Hua-Li
Lai, Lu-Ying
Xu, Rui
Xu, Shi-Yuan
author_facet Liu, Zhong-Jie
Zhao, Wei
Lei, Hong-Yi
Xu, Hua-Li
Lai, Lu-Ying
Xu, Rui
Xu, Shi-Yuan
author_sort Liu, Zhong-Jie
collection PubMed
description Bupivacaine, a typical local anesthetic, induces neurotoxicity via reactive oxygen species regulation of apoptosis. High glucose could enhance bupivacaine-induced neurotoxicity through regulating oxidative stress, but the mechanism of it is not clear. Mitochondrial calcium uniporter (MCU), a key channel for regulating the mitochondrial Ca(2+) (mCa(2+)) influx, is closely related to oxidative stress via disruption of mCa(2+) homeostasis. Whether MCU is involved in high glucose-sensitized bupivacaine-induced neurotoxicity remains unknown. In this study, human neuroblastoma (SH-SY5Y) cells were cultured with high glucose and/or bupivacaine, and the data showed that high glucose enhanced bupivacaine-induced MCU expression elevation, mCa(2+) accumulation, and oxidative damage. Next, Ru360, an inhibitor of MCU, was employed to pretreated SH-SY5Y cells, and the results showed that it could decrease high glucose and bupivacaine-induced mCa(2+) accumulation, oxidative stress, and apoptosis. Further, with the knockdown of MCU with a specific small interfering RNA (siRNA) in SH-SY5Y cells, we found that it also could inhibit high glucose and bupivacaine-induced mCa(2+) accumulation, oxidative stress, and apoptosis. We propose that downregulation expression or activity inhibition of the MCU channel might be useful for restoring the mitochondrial function and combating high glucose and bupivacaine-induced neurotoxicity. In conclusion, our study demonstrated the crucial role of MCU in high glucose-mediated enhancement of bupivacaine-induced neurotoxicity, suggesting the possible use of this channel as a target for curing bupivacaine-induced neurotoxicity in diabetic patients.
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spelling pubmed-63980172019-03-25 High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells Liu, Zhong-Jie Zhao, Wei Lei, Hong-Yi Xu, Hua-Li Lai, Lu-Ying Xu, Rui Xu, Shi-Yuan Oxid Med Cell Longev Research Article Bupivacaine, a typical local anesthetic, induces neurotoxicity via reactive oxygen species regulation of apoptosis. High glucose could enhance bupivacaine-induced neurotoxicity through regulating oxidative stress, but the mechanism of it is not clear. Mitochondrial calcium uniporter (MCU), a key channel for regulating the mitochondrial Ca(2+) (mCa(2+)) influx, is closely related to oxidative stress via disruption of mCa(2+) homeostasis. Whether MCU is involved in high glucose-sensitized bupivacaine-induced neurotoxicity remains unknown. In this study, human neuroblastoma (SH-SY5Y) cells were cultured with high glucose and/or bupivacaine, and the data showed that high glucose enhanced bupivacaine-induced MCU expression elevation, mCa(2+) accumulation, and oxidative damage. Next, Ru360, an inhibitor of MCU, was employed to pretreated SH-SY5Y cells, and the results showed that it could decrease high glucose and bupivacaine-induced mCa(2+) accumulation, oxidative stress, and apoptosis. Further, with the knockdown of MCU with a specific small interfering RNA (siRNA) in SH-SY5Y cells, we found that it also could inhibit high glucose and bupivacaine-induced mCa(2+) accumulation, oxidative stress, and apoptosis. We propose that downregulation expression or activity inhibition of the MCU channel might be useful for restoring the mitochondrial function and combating high glucose and bupivacaine-induced neurotoxicity. In conclusion, our study demonstrated the crucial role of MCU in high glucose-mediated enhancement of bupivacaine-induced neurotoxicity, suggesting the possible use of this channel as a target for curing bupivacaine-induced neurotoxicity in diabetic patients. Hindawi 2019-02-18 /pmc/articles/PMC6398017/ /pubmed/30911349 http://dx.doi.org/10.1155/2019/7192798 Text en Copyright © 2019 Zhong-Jie Liu et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Zhong-Jie
Zhao, Wei
Lei, Hong-Yi
Xu, Hua-Li
Lai, Lu-Ying
Xu, Rui
Xu, Shi-Yuan
High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells
title High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells
title_full High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells
title_fullStr High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells
title_full_unstemmed High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells
title_short High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells
title_sort high glucose enhances bupivacaine-induced neurotoxicity via mcu-mediated oxidative stress in sh-sy5y cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398017/
https://www.ncbi.nlm.nih.gov/pubmed/30911349
http://dx.doi.org/10.1155/2019/7192798
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