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电子烟诱导的大麻二酚(CBD)氧化产物 CBD 醌与 KEAP1 形成蛋白加合物,并激活 KEAP1-Nrf2 基因。

Vaping Induced Cannabidiol (CBD) Oxidation Product CBD Quinone Forms Protein Adducts with KEAP1 and Activates KEAP1-Nrf2 Genes.

机构信息

Curriculum in Toxicology and Environmental Medicine, Center for Environmental Medicine, Asthma, and Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.

出版信息

Chem Res Toxicol. 2023 Apr 17;36(4):565-569. doi: 10.1021/acs.chemrestox.3c00038. Epub 2023 Mar 31.

DOI:10.1021/acs.chemrestox.3c00038
PMID:36999736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10966663/
Abstract

Cannabidiol (CBD) vaping products have become widely available in the U.S. since their legalization in 2018. However, little is known about their respiratory health effects. Here we show that aerosolization of commercial CBD vaping products generates a reactive CBD quinone (CBDQ) which forms adducts with protein cysteine residues. Using click chemistry and a novel vaping product exposure system (VaPES), we further demonstrate that CBDQ forms adducts with human bronchial epithelial cell proteins including Keap1 and activates KEAP1-Nrf2 stress response pathway genes. These results suggest that vaping CBD alters protein function and induces cellular stress pathways in the lung.

摘要

自从 2018 年大麻二酚(CBD)雾化产品合法化以来,它们已在美国广泛销售。然而,关于其对呼吸道健康的影响知之甚少。在这里,我们表明,商业 CBD 雾化产品的雾化会产生一种具有反应性的 CBD 醌(CBDQ),它与蛋白质半胱氨酸残基形成加合物。使用点击化学和一种新型的雾化产品暴露系统(VaPES),我们进一步表明,CBDQ 与人支气管上皮细胞蛋白形成加合物,包括 Keap1 并激活 KEAP1-Nrf2 应激反应途径基因。这些结果表明,吸食 CBD 会改变肺部蛋白质的功能并诱导细胞应激途径。

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本文引用的文献

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The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.电子烟或蒸气产品使用相关肺损伤流行:发病机制、管理和未来方向:美国胸科学会官方研讨会报告。
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Vaping additives cannabinoid oil and vitamin E acetate adhere to and damage the human airway epithelium.蒸气添加剂大麻素油和维生素 E 醋酸盐附着并损伤人体气道上皮。
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Formation of Redox-Active Duroquinone from Vaping of Vitamin E Acetate Contributes to Oxidative Lung Injury.电子烟油中的维生素 E 醋酸酯形成氧化还原活性的二氢醌,导致氧化肺损伤。
Chem Res Toxicol. 2022 Feb 21;35(2):254-264. doi: 10.1021/acs.chemrestox.1c00309. Epub 2022 Jan 25.
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Biomolecules. 2021 Jul 5;11(7):991. doi: 10.3390/biom11070991.
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