PDF(Pubmed)
Abstract：
People are exposed to high concentrations of antibacterial agent cetylpyridinium chloride (CPC) via food and personal care products, despite little published information regarding CPC effects on eukaryotes. Here, we show that low-micromolar CPC exposure, which does not cause cell death, inhibits mitochondrial ATP production in primary human keratinocytes, mouse NIH-3T3 fibroblasts, and rat RBL-2H3 immune mast cells. ATP inhibition via CPC (EC50 1.7 μM) is nearly as potent as that caused by canonical mitotoxicant CCCP (EC50 1.2 μM). CPC inhibition of oxygen consumption rate (OCR) tracks with that of ATP: OCR is halved due to 1.75 μM CPC in RBL-2H3 cells and 1.25 μM in primary human keratinocytes. Mitochondrial [Ca2+] changes can cause mitochondrial dysfunction. Here we show that CPC causes mitochondrial Ca2+ efflux from mast cells via an ATP-inhibition mechanism. Using super-resolution microscopy (fluorescence photoactivation localization) in live cells, we have discovered that CPC causes mitochondrial nanostructural defects in live cells within 60 min, including the formation of spherical structures with donut-like cross section. This work reveals CPC as a mitotoxicant despite widespread use, highlighting the importance of further research into its toxicological safety.
摘要：
人们通过食品和个人护理产品接触高浓度的抗菌剂氯化十六烷基吡啶(CPC),尽管有关CPC对真核生物的影响的信息很少。这里,我们表明低微摩尔CPC暴露，不会导致细胞死亡，抑制原代人角质形成细胞中线粒体ATP的产生，小鼠NIH-3T3成纤维细胞，和大鼠RBL-2H3免疫肥大细胞。通过CPC（EC501.7μM）的ATP抑制几乎与经典有丝分裂毒素CCCP（EC501.2μM）引起的抑制一样有效。CPC对耗氧率（OCR）的抑制作用与ATP的抑制作用：由于RBL-2H3细胞中的1.75μMCPC和原代人角质形成细胞中的1.25μM，OCR减半。线粒体[Ca2+]改变可引起线粒体功能障碍。在这里，我们显示CPC通过ATP抑制机制导致线粒体Ca2+从肥大细胞流出。在活细胞中使用超分辨率显微镜（荧光光活化定位），我们发现CPC在60分钟内导致活细胞线粒体纳米结构缺陷，包括具有甜甜圈状横截面的球形结构的形成。这项工作揭示了CPC作为一种丝裂毒素，尽管它被广泛使用，强调进一步研究其毒理学安全性的重要性。
