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Citation
Tags
HERO ID
3981501
Reference Type
Journal Article
Title
High perfluorooctanoic acid exposure induces autophagy blockage and disturbs intracellular vesicle fusion in the liver
Author(s)
Yan, S; Zhang, H; Guo, X; Wang, J; Dai, J
Year
2017
Is Peer Reviewed?
Yes
Journal
Archives of Toxicology
ISSN:
0340-5761
EISSN:
1432-0738
Volume
91
Issue
1
Page Numbers
247-258
Language
English
PMID
26879310
DOI
10.1007/s00204-016-1675-1
Web of Science Id
WOS:000392320700015
Relationship(s)
is supplemented by
3986361
: Supplementary materials
Abstract
Perfluorooctanoic acid (PFOA) has been shown to cause hepatotoxicity and other toxicological effects. Though PPARα activation by PFOA in the liver has been well accepted as an important mechanism of PFOA-induced hepatotoxicity, several pieces of evidence have shown that the hepatotoxic effects of PFOA may not be fully explained by PPARα activation. In this study, we observed autophagosome accumulation in mouse livers as well as HepG2 cells after PFOA exposure. Further in vitro study revealed that the accumulation of autophagosomes was not caused by autophagic flux stimulation. In addition, we observed that PFOA exposure affected the proteolytic activity of HepG2 cells while significant dysfunction of lysosomes was not detected. Quantitative proteomic analysis of crude lysosomal fractions from HepG2 cells treated with PFOA revealed that 54 differentially expressed proteins were related to autophagy or vesicular trafficking and fusion. The proteomic results were further validated in the cells in vitro and livers in vivo after PFOA exposure, which implied potential dysfunction at the late stage of autophagy. However, in HepG2 cells, it seemed that further inhibition of autophagy did not significantly alter the effects of PFOA on cell viability. Although these findings demonstrate that PFOA blocked autophagy and disturbed intracellular vesicle fusion in the liver, the changes in autophagy were observed only at high cytotoxic concentrations of PFOA, suggesting that autophagy may not be a primary target or mode of toxicity. Furthermore, since altered liver autophagy was not observed at concentrations of PFOA associated with human exposures, the relevance of these findings must be questioned.
Keywords
Perfluorooctanoic acid, Autophagy, Proteome, Vesicle fusion
Tags
PFAS
•
Additional PFAS (formerly XAgency)
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
PubMed
Not prioritized for screening
Potassium perfluorooctanoate
Sodium perfluorooctanoate
•
^Per- and Polyfluoroalkyl Substances (PFAS)
PFOA (335-67-1) and PFOS (1763-23-1)
Literature Search – Adverse outcome pathway (2015-present)
Pubmed
WOS
•
PFAS 150
Literature Search August 2019
PubMed
Web of Science
Not prioritized for screening
Ammonium perfluorooctanoate
Perfluorooctanoic acid
•
PFNA
Litsearch Update 2017-2018
Toxline
Literature Search
Toxline
PFNA May 2019 Update
Toxnet
Title and Abstract Screening
Full Text Screening
Excluded
Not PFNA
•
PFOA (335-67-1) and PFOS (1763-23-1)
Literature Search – Adverse outcome pathway (2015-present)
Pubmed
WOS
Screening Results
In vivo animal studies
Liver tox
In vitro/ex vivo/in silico
-omics (general)
Other mechanistic studies
Literature Search Update (2013-2019)
PubMed
WOS
•
PFOA and PFOS OW MCLG Approaches
Cited in White Papers
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