Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells
	Wan, Bin; Xin, Yan; Yang, Yu; Cui, Xue-Jing; Xie, Yi-Chun; Guo, Liang-Hong
刊名	ARCHIVES OF TOXICOLOGY
	2018-10-01
卷号	92 期号:10 页码:3131-3147
关键词	PFAAs Mitophagy ER-phagy Lung toxicity
ISSN号	0340-5761
文献子类	Article
英文摘要	Wide application of perfluoroalkyl acids (PFAAs) has raised great concerns on their side-effects on human health. PFAAs have been shown to accumulate mainly in the liver and cause hepatotoxicity. However, PFAAs can also deposit in lung tissues through air-borne particles and cause serious pulmonary toxicity. But the underlying mechanisms are still largely unknown. Autophagy is a type of programmed cell death parallel to necrosis and apoptosis, and may be involved in the lung toxicity of PFAAs. In this study, lung cancer cells, A549, were employed as the model to investigate the effects of three PFAAs with different carbon chain lengths on cell autophagy. Through Western blot analysis on LC3-I/II ratio of cells exposed to non-cytotoxic concentration (200 mu M) and cytotoxic concentration (350 mu M), we found concentration-dependent increase of autophagosomes in cells, which was further confirmed by TEM examination on ultra-thin section of cells and fluorescence imaging on autophagosomes in live cells. The abundance of p62 increased with the PFAAs concentration indicating the blockage of autophagy flux. Furthermore, we identified the mitochondrial autophagy (mitophagy) and endoplasmic reticulum autophagy (ER-phagy) morphologically as the major types of autophagy, suggesting the disruption on mitochondria and ERs. These organelle damages were confirmed by the overgeneration of ROS, hyperpolarization of mitochondrial membrane potential, as well as the up-regulation of ER-stress-related proteins, ATF4 and p-IRE1. Further analysis on the signaling pathways showed that PFAAs activated the MAPK pathways and inhibited the PI3K/Akt pathway, with potencies following the order of PFDA > PFNA > PFOA. Anti-oxidant (NAC) treatment did not rescue cells from death, indicating that oxidative stress is not the reason of cytotoxicity. Inhibition of autophagy by Atg5 siRNA and chloroquine even increased the toxicity of PFAAs, suggesting that PFAAs-autophagy was induced as the secondary effects of organelle damages and played a protective role during cell death.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/41009]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Wan, Bin,Xin, Yan,Yang, Yu,et al. Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells[J]. ARCHIVES OF TOXICOLOGY,2018,92(10):3131-3147.
APA	Wan, Bin,Xin, Yan,Yang, Yu,Cui, Xue-Jing,Xie, Yi-Chun,&Guo, Liang-Hong.(2018).Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells.ARCHIVES OF TOXICOLOGY,92(10),3131-3147.
MLA	Wan, Bin,et al."Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells".ARCHIVES OF TOXICOLOGY 92.10(2018):3131-3147.