ArticleScientific reports2017
HIF-1-mediated suppression of mitochondria electron transport chain function confers resistance to lidocaine-induced cell death.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- Anesthesia and mitochondria: balancing toxicity and protection through emerging therapeutic strategies.Journal of anesthesia · 2026Review
- Intersection Between Local Anesthetics and Cancer Biology: What Now? Where Are We Going?Advanced biology · 2025Review
- NIR-responsive bio-system with sequential antibacterial and immunomodulatory effects for the treatment of periodontitis.Bioactive materials · 2025Article
- Genetic Variation and Sex-Based Differences: Current Considerations for Anesthetic Management.Current issues in molecular biology · 2025Review
- Quercetin relieves compression-induced cell death and lumbar disc degeneration by stabilizing HIF1A protein.Heliyon · 2024Article
- Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed.International journal of molecular sciences · 2022Review
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
- MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity.The Journal of experimental medicine · 2022Article
- Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells.Metabolites · 2022Article
- Review
- Mitochondria bridge HIF signaling and ferroptosis blockage in acute kidney injury.Cell death & disease · 2022Review
- Enhanced glucose metabolism through activation of HIF-1α covers the energy demand in a rat embryonic heart primordium after heartbeat initiation.Scientific reports · 2022Article
- Mechanism of Hypoxia-Mediated Smooth Muscle Cell Proliferation Leading to Vascular Remodeling.BioMed research international · 2022Review
- Protective Effect ofDrug design, development and therapy · 2022Article
- GPR120 Inhibits Colitis Through Regulation of CD4Gastroenterology · 2022Article
- Metabolomic Impact of Lidocaine on a Triple Negative Breast Cancer Cell Line.Frontiers in pharmacology · 2022Article
- Article
- Review
- Reduction in mitochondrial oxidative stress mediates hypoxia-induced resistance to cisplatin in human transitional cell carcinoma cells.Neoplasia (New York, N.Y.) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The local anesthetic lidocaine induces cell death by altering reactive oxygen species (ROS) generation and mitochondrial electron transport chain function. Because hypoxia-inducible factor 1 (HIF-1) is involved in determining oxygen metabolism and mitochondria function, we investigated the involvement of HIF-1 activity in lidocaine-induced cell death. We investigated the role of HIF activation on lidocaine-induced caspase activation and cell death in renal cell-derived RCC4 cells lacking functional von Hippel-Lindau (VHL) protein. We demonstrate that HIF-1 suppressed oxygen consumption and facilitated glycolysis in a pyruvate dehydrogenase kinase-1-dependent manner and that activation of HIF-1 conferred resistance to lidocaine-induced cell death. We also demonstrated that exogenous HIF-1 activation, through HIFα-hydroxylase inhibition or exposure to hypoxic conditions, alleviates lidocaine toxicity by suppressing mitochondria function and generating ROS, not only in RCC4 cells, but also in the neuronal SH-SY5Y cells. In conclusion, we demonstrate that HIF-1 activation due to VHL deletion, treatment with small molecule HIFα-hydroxylase inhibitors, and exposure to hypoxic conditions suppresses mitochondrial respiratory chain function and confers resistance to lidocaine toxicity.
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