ArticleJournal of cellular and molecular medicine2017
Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Quercetin attenuated ropivacaine-induced neurotoxicity in SH-SY5Y cells through upregulating Pim1 and enhancing autophagy.Heliyon · 2024Article
- The role of kinases in peripheral nerve regeneration: mechanisms and implications.Frontiers in neurology · 2024Review
- The potential anti-tumor effect of anesthetics on cancer by regulating autophagy.Frontiers in pharmacology · 2024Review
- Oxidative DNA Damage-induced PARP-1-mediated Autophagic Flux Disruption Contributes to Bupivacaine-induced Neurotoxicity During Pregnancy.Current neuropharmacology · 2023Article
- Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Melatonin Attenuates Ropivacaine-Induced Apoptosis by Inhibiting Excessive Mitophagy Through the Parkin/PINK1 Pathway in PC12 and HT22 Cells.Inflammation · 2022Article
- Intervention of NF-Κb Signaling Pathway and Preventing Post-Operative Cognitive Dysfunction as Well as Neuronal Apoptosis.Iranian journal of public health · 2022Article
- Article
- Mystery of methamphetamine-induced autophagosome accumulation in hippocampal neurons: loss of syntaxin 17 in defects of dynein-dynactin driving and autophagosome-late endosome/lysosome fusion.Archives of toxicology · 2021Article
- Amitriptyline Protects Against Lidocaine-induced Neurotoxicity in SH-SY5Y Cells via Inhibition of BDNF-mediated Autophagy.Neurotoxicity research · 2021Article
- Lidocaine promotes autophagy of SH-SY5Y cells through inhibiting PI3K/AKT/mTOR pathway by upregulating miR-145.Toxicology research · 2020Article
- The TSPO-specific Ligand PK11195 Protects Against LPS-Induced Cognitive Dysfunction by Inhibiting Cellular Autophagy.Frontiers in pharmacology · 2020Article
- Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model.Neurochemical research · 2019Article
- Lidocaine induces protective autophagy in rat C6 glioma cell line.International journal of oncology · 2019Article
- Ropivacaine mesylate exerts neurotoxicity via up-regulation of Fas/FasL expression in rat pheochromocytoma PC12 cells.American journal of translational research · 2019Article
- Tetramethylpyrazine attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells through regulating apoptosis, autophagy and oxidative damage.Drug design, development and therapy · 2019Article
- Protective effects of extracellular polymeric substances fromExperimental and therapeutic medicine · 2018Article
- Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model.Metabolic brain disease · 2018Article
- Osthole-Mediated Inhibition of Neurotoxicity Induced by Ropivacaine via Amplification of the Cyclic Adenosine Monophosphate Signaling Pathway.Dose-response : a publication of International Hormesis SocietyArticle
- [Autophagy activation attenuates the neurotoxicity of local anaesthetics by decreasing caspase-3 activity in rats].Brazilian journal of anesthesiology (Elsevier)Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma SH-SY5Y cells. Neurotoxicity was evaluated by MTT assay, morphological alterations and median death dosage. Autophagic flux was estimated by autolysosome formation (dual fluorescence LC3 assay), LC3-II generation and p62 protein degradation (immunoblotting). Signalling alterations were examined by immunoblotting analysis. Inhibition of autophagy was achieved by transfection with beclin-1 siRNA. We observed that LAs decreased cell viability in a dose-dependent manner. The neurotoxicity of LAs was tetracaine > bupivacaine > ropivacaine > procaine > lidocaine. LAs increased autophagic flux, as reflected by increases in autolysosome formation and LC3-II generation, and decrease in p62 levels. Moreover, LAs inhibited tuberin/mTOR/p70S6K signalling, a negative regulator of autophagy activation. Most importantly, autophagy inhibition by beclin-1 knockdown exacerbated the LAs-provoked cell damage. Our data suggest that autophagic flux was up-regulated by LAs through inhibition of tuberin/mTOR/p70S6K signalling, and autophagy activation served as a protective mechanism against LAs neurotoxicity. Therefore, autophagy manipulation could be an alternative therapeutic intervention to prevent LAs-induced neuronal damage.
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