全氟癸酸（PFDA）通过抑制线粒体β-氧化增加氧化应激。
Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation.
作者信息
Widhalm Raimund, Granitzer Sebastian, Natha Benjamin, Zoboli Ottavia, Derx Julia, Zeisler Harald, Salzer Hans, Weiss Stefan, Schmitner Nicole, Kimmel Robin A, Österreicher Tamina, Oberle Raimund, Hengstschläger Markus, Distel Martin, Gundacker Claudia
机构信息
Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; Exposome Austria, Research Infrastructure and National EIRENE Hub, Austria.
Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; Exposome Austria, Research Infrastructure and National EIRENE Hub, Austria.
出版信息
Environ Pollut. 2025 Feb 15;367:125595. doi: 10.1016/j.envpol.2024.125595. Epub 2024 Dec 27.
Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic chemicals that are ubiquitous environmental pollutants. Among PFAS, perfluorodecanoic acid (PFDA) is one of the most toxic compounds, but the molecular basis behind its toxicity is not fully understood. In an interspecies comparison with placental cells (HTR-8/SVneo) and zebrafish embryos, we demonstrate that PFDA induces mitochondrial dysfunction and impairs fatty acid β-oxidation. Reduced β-oxidation leads to less TCA cycle activity, resulting in less NADH and consequently NADPH production. Thereby NADPH-dependent glutathione recycling is impaired, increasing cellular oxidative stress that can only be partially compensated by NRF2 activation.
全氟和多氟烷基物质（PFAS）是一大类合成有机化学品，是普遍存在的环境污染物。在PFAS中，全氟癸酸（PFDA）是毒性最强的化合物之一，但其毒性背后的分子机制尚未完全明确。在与胎盘细胞（HTR-8/SVneo）和斑马鱼胚胎的种间比较中，我们证明PFDA会诱导线粒体功能障碍并损害脂肪酸β氧化。β氧化减少导致三羧酸循环活性降低，进而使NADH生成减少，最终导致NADPH生成减少。由此，依赖NADPH的谷胱甘肽循环受损，增加了细胞氧化应激，而NRF2激活只能部分补偿这种应激。
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