High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells.
Oxid Med Cell Longev
; 2019: 7192798, 2019.
Article
em En
| MEDLINE
| ID: mdl-30911349
ABSTRACT
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 Ca2+ (mCa2+) influx, is closely related to oxidative stress via disruption of mCa2+ 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, mCa2+ 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 mCa2+ 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 mCa2+ 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bupivacaína
/
Canais de Cálcio
/
Estresse Oxidativo
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Glucose
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Neurotoxinas
Limite:
Humans
Idioma:
En
Revista:
Oxid Med Cell Longev
Assunto da revista:
METABOLISMO
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China