Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-211 Gdańsk, Poland.
Toxicol Appl Pharmacol. 2011 Mar 1;251(2):163-8. doi: 10.1016/j.taap.2011.01.002. Epub 2011 Jan 12.
The global distribution of perfluorinated acids (PFAs) in industry and in household is well known. Their increasing environmental occurrence and biomagnification in the living organisms have drawn growing interests in efforts to describe precisely the mechanisms of action in vitro and in vivo. Our previous investigations widely described lipophilicity-dependent cytotoxicity of PFAs as well as the effect of perfluorination of carbon chain on depolarization of plasma membrane potential, acidification or mitochondrial dysfunctions. In this study we presented in dose- and time-dependent manner the impact of PFAs on calcium homeostasis in HCT116 cells. Comparative analysis of cytosolic Ca²+ and mitochondrial calcium Ca²+ carried out by flow cytometry revealed distinct uptake of calcium into mitochondria in correlation to increasing lipophilicity of PFAs. Massive accumulation of Ca²+ was not accompanied by equivalent loss of Ca²+. Indeed, moderate changes of Ca²+ were observed after incubation with 400 μM PFDoDA reaching 29.83% and 49.17% decrease at 4th and 72nd hour, respectively. At the same time, mitochondrial calcium uptake increased from 2- to more than 4-fold comparing with non-treated cells. Incubation with non-fluorinated decanoic acid (DA) did not cause any changes in calcium homeostasis. Presented data show that PFAs-induced perturbations in calcium distribution seem to be a missing link related to mitochondria dysfunction playing a crucial role in determination of apoptotic cell death. Complete scheme for the mechanism of cytotoxic action of PFAs has been included.
全氟酸（PFA）在工业和家庭中的全球分布是众所周知的。它们在环境中的出现频率不断增加，以及在生物体内的生物放大作用，引起了人们越来越多的兴趣，促使人们努力精确描述体外和体内作用机制。我们之前的研究广泛描述了 PFA 的脂溶性依赖性细胞毒性，以及碳链全氟化对质膜电位去极化、酸化或线粒体功能障碍的影响。在这项研究中，我们以剂量和时间依赖的方式展示了 PFA 对 HCT116 细胞钙稳态的影响。通过流式细胞术对细胞质[Ca²+]（c）和线粒体钙[Ca²+]（m）进行的比较分析表明，PFA 的脂溶性与钙向线粒体的摄取呈正相关。大量[Ca²+]（m）的积累并没有伴随着细胞质[Ca²+]（c）的相应损失。事实上，在用 400 μM PFDoDA 孵育后，观察到细胞质[Ca²+]（c）的中度变化，在第 4 小时和第 72 小时分别达到 29.83%和 49.17%的下降。与此同时，线粒体钙摄取与未经处理的细胞相比增加了 2 到 4 倍以上。用非氟化癸酸（DA）孵育不会引起钙稳态的任何变化。目前的数据表明，PFA 诱导的钙分布紊乱似乎是与线粒体功能障碍相关的缺失环节，在确定细胞凋亡死亡中起着关键作用。已经包括了 PFA 细胞毒性作用机制的完整方案。
