Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization.
Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization.
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药剂氯化十六烷基吡啶通过干扰钙动员来抑制免疫肥大细胞功能。
DOI：
10.1016/j.fct.2023.113980
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Gosse,JulieA
中科院分区：
文献类型：
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作者：
Obeng,Bright;Potts,ChristianM;West,BaileyE;Burnell,JohnE;Fleming,PatrickJ;Shim,JuyoungK;Kinney,MarissaS;Ledue,EmilyL;Sangroula,Suraj;BaezVazquez,AlanY;Gosse,JulieA
氯化十六烷基吡啶（CPC）是一种抗菌剂，以毫摩尔浓度用于许多个人护理和清洁产品以及供人类消费的食品。关于CPC的真核毒理学信息极少。我们研究了CPC对免疫细胞型肥大细胞信号转导的影响。在这里，我们表明，CPC抑制肥大细胞功能脱粒与抗原剂量依赖性和非细胞毒性剂量低于1000倍的消费品中的浓度。之前我们表明CPC会破坏4，5-二磷酸磷脂酰肌醇，这是一种对钙池操纵的Ca 2+进入（SOCE）至关重要的信号脂质，它介导脱颗粒。我们的研究结果表明，CPC抑制抗原刺激的SOCE：CPC限制Ca 2+流出内质网，减少Ca 2+摄取到线粒体，并抑制Ca 2+流经质膜通道。虽然抑制钙离子通道功能可以引起质膜电位（PMP）和胞质pH值的改变，CPC不影响PMP或pH值。抑制SOCE是已知的抑制微管聚合，在这里，我们表明，CPC确实剂量依赖性地关闭形成微管tracks.In体外数据显示，CPC抑制微管不是由于直接CPC干扰微管蛋白。总之，CPC是一种靶向Ca 2+动员的信号毒物。
Cetylpyridinium chloride (CPC) is an antimicrobial used in numerous personal care and janitorial products and food for human consumption at millimolar concentrations. Minimal information exists on the eukaryotic toxicology of CPC. We have investigated the effects of CPC on signal transduction of the immune cell type mast cells. Here, we show that CPC inhibits the mast cell function degranulation with antigen dose-dependence and at non-cytotoxic doses ∼1000-fold lower than concentrations in consumer products. Previously we showed that CPC disrupts phosphatidylinositol 4,5-bisphosphate, a signaling lipid critical for store-operated Ca2+entry (SOCE), which mediates degranulation. Our results indicate that CPC inhibits antigen-stimulated SOCE: CPC restricts Ca2+efflux from endoplasmic reticulum, reduces Ca2+uptake into mitochondria, and dampens Ca2+flow through plasma membrane channels. While inhibition of Ca2+channel function can be caused by alteration of plasma membrane potential (PMP) and cytosolic pH, CPC does not affect PMP or pH. Inhibition of SOCE is known to depress microtubule polymerization, and here we show that CPC indeed dose-dependently shuts down formation of microtubule tracks.In vitrodata reveal that CPC inhibition of microtubules is not due to direct CPC interference with tubulin. In summary, CPC is a signaling toxicant that targets Ca2+mobilization.