Lidocaine depolarizes the mitochondrial membrane potential by intracellular alkalization in rat dorsal root ganglion neurons

Onizuka, Shin; Yonaha, Tetsu; Tamura, Ryuji; Kasiwada, Masatoshi; Shirasaka, Toshiro; Tsuneyoshi, Isao

doi:10.1007/s00540-010-1079-y

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…Lidocaine has been recognized to induce apoptotic cell death in human neuroblastoma cells (Friederich and Schmitz 2002), and the mitochondrial pathway was recognized to get involved in the lidocaine-induced apoptosis (Johnson et al 2004;Onizuka et al 2010Onizuka et al , 2011Werdehausen et al 2007). Recently, the ER stress has also been confirmed to involve in the lidocaine-induced apoptosis of rat adrenal pheochromocytoma PC12 cells (Hong et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Lidocaine has been indicated to induce morphological changes such as cell axon collapse and cell swelling (Kasaba et al 2003;Onizuka et al 2005) and to promote apoptosis through the mitochondrial pathway (Johnson et al 2004;Onizuka et al 2010Onizuka et al , 2011Werdehausen et al 2007) and even necrosis (Lawrence et al 1966;Onizuka et al 2012;Yagiela et al 1982). And the promotion to apoptosis or necrosis is not associated with the block of voltage-gated sodium channel, which is the main target of lidocaine, for its anesthetic effect.…”

Section: Introductionmentioning

confidence: 99%

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Endoplasmic Reticulum Stress Is Involved in the Lidocaine-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells

Han

2014

J Mol Neurosci

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Lidocaine has been indicated to promote apoptosis and to promote endoplasmic reticulum (ER) stress. However, the mechanism underlining ER stress-mediated apoptosis is unclear. In the present study, we investigated the promotion to ER stress in the lidocaine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Firstly, we confirmed that lidocaine treatment induced apoptosis in SH-SY5Y cells, time-dependently and dose-dependently, via MTT cell viability assay and annexin V/FITC apoptosis detection with a FACScan flow cytometer. And the anti-apoptosis Bcl-2 and Bcl-xL were downregulated, whereas the apoptosis-executive caspase 3 was promoted through Western blot assay and caspase 3 activity assay. Moreover, the ER stress-associated binding immunoglobulin protein (BiP), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein homologous protein (CHOP) were also upregulated at both mRNA and protein levels by lidocaine treatment. On the other hand, downregulation of the ER stress-associated BiP by RNAi method not only blocked the lidocaine-promoted ER stress but also attenuated the lidocaine-induced SH-SY5Y cell apoptosis. In conclusion, the present study confirmed the involvement of ER stress in the lidocaine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Our study provides a better understanding on the mechanism of lidocaine's neurovirulence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Is Involved in the Lidocaine-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells

Han

2014

J Mol Neurosci

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“…Besides epidemiological research, extensive rapid accumulation of α-synuclein was reported in swollen axons in brain tissues from cases who died after TBI (Uryu et al, 2007). In experimental animals, TBI can induce the accumulation of α-synuclein (Uryu et al, 2003), neuroinflammatory response (Morales et al, 2005), progressive loss of nigrostriatal dopaminergic neurons (Hutson et al, 2011), and a reduction in tyrosine hydroxylase activity in the striatum (Onizuka et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to paraquat: mitochondrial dysfunction and oxidative stress

et al. 2014

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Recent studies suggest that traumatic brain injury (TBI) and pesticide exposure increase the risk of Parkinson’s disease (PD), but the molecular mechanisms involved remain unclear. Using an in vitro model of TBI, we evaluated the role of mitochondrial membrane potential (ΔΨm) and mitochondrial reactive oxygen species (ROS) induced by stretch on dopaminergic cell death upon paraquat exposure. Human dopaminergic neuroblastoma SH-SY5Y cells grown on silicone membrane were stretched at mild (25%) and moderate (50%) strain prior to paraquat exposure. We observed that moderate stretch (50% strain) increased the vulnerability of cells to paraquat demonstrated by the loss of plasma membrane integrity (propidium iodide-uptake) and decreased mitochondrial activity (MTT assay). Mitochondrial depolarization occurred immediately after stretch, while mitochondrial ROS increased rapidly and remained elevated for up to 4 h after the stretch injury. Intracellular glutathione (GSH) stores were also transiently decreased immediately after moderate stretch. Cells treated with paraquat, or moderate stretch exhibited negligible mitochondrial depolarization at 48 h post treatment, whereas in cells stretched prior to paraquat exposure, a significant mitochondrial depolarization occurred compared to samples exposed to either paraquat or stretch. Moderate stretch also increased mitochondrial ROS formation, as well as exacerbated intracellular GSH loss induced by paraquat. Overexpression of manganese superoxide dismutase (MnSOD) markedly diminished the deleterious effects of stretch in paraquat neurotoxicity. Our findings demonstrate that oxidative stress induced by mitochondrial dysfunction plays a critical role in the synergistic toxic effects of stretch (TBI) and pesticide exposure. Mitigation of oxidative stress via mitochondria-targeted antioxidants appears an attractive route for treatment of neurodegeneration mediated by TBI.

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“…That is, the toxicity depends not only on the concentration but also on the cell type. In addition, there are several case reports of cell damage (muscle, cartilage) at clinically relevant concentrations12345678. Although toxicity caused by clinically relevant concentrations is rare, it may produce severe complications when it occurs.…”

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confidence: 99%

Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

Zhao

et al. 2017

Sci Rep

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Local anaesthetics (LAs) may lead to neurological complications, but the underlying mechanism is still unclear. Many neurotoxicity research studies have examined different LAs, but none have comprehensively explored the distinct mechanisms of neurotoxicity caused by amide- (bupivacaine) and ester- (procaine) type LAs. Here, based on a CCK8 assay, LDH assay, Rhod-2-AM and JC-1 staining, 2′,7′-dichlorohy-drofluorescein diacetate and dihydroethidium probes, an alkaline comet assay, and apoptosis assay, we show that both bupivacaine and procaine significantly induce mitochondrial calcium overload and a decline in the mitochondrial membrane potential as well as overproduction of ROS, DNA damage and apoptosis (P < 0.05). There were no significant differences in mitochondrial injury and apoptosis between the bupivacaine and procaine subgroups (P > 0.05). However, to our surprise, the superoxide anionic level after treatment with bupivacaine, which leads to more severe DNA damage, was higher than the level after treatment with procaine, while procaine produced more peroxidation than bupivacaine. Some of these results were also affirmed in dorsal root ganglia neurons of C57 mice. The differences in the superoxidation and peroxidation induced by these agents suggest that different types of LAs may cause neurotoxicity via different pathways. We can target more accurate treatment based on their different mechanisms of neurotoxicity.

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Lidocaine depolarizes the mitochondrial membrane potential by intracellular alkalization in rat dorsal root ganglion neurons

Abstract: These results demonstrated that lidocaine depolarizes ΔΨm by intracellular alkalization. These results may indicate one of the mechanisms responsible for lidocaine-induced neurotoxicity.

Cited by 23 publications

References 41 publications

Endoplasmic Reticulum Stress Is Involved in the Lidocaine-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells

Endoplasmic Reticulum Stress Is Involved in the Lidocaine-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells

Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to paraquat: mitochondrial dysfunction and oxidative stress

Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

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