title: Perfluorooctane sulfonate blocked autophagy flux and induced lysosome membrane permeabilization in HepG2 cells.
abstract: Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant widely distributed in the environment, wildlife and human. In this study, as observed under the transmission electron microscope, PFOS increased autophagosome numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western blot analysis. PFOS increased P62 level and chloroquine failed to further increase the expression of LC3-II after PFOS treatment, indicating that the accumulation of autophagosome was due to impaired degradation rather than increased formation. With acridine orange staining, we found PFOS caused lysosomal membrane permeabilization (LMP). In this study, autophasome formation inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy stimulator rapamycin further decreased cell viability and increased LDH release, cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells significantly. These further supported the notion that autophagic cell death contributed to PFOS-induced hepatotoxicity. In summary, the data of the present study revealed that PFOS induced LMP and consequent blockage of autophagy flux, leading to an excessive accumulation of the autophagosomes and turning autophagy into a destructive process eventually. This finding will provide clues for effective prevention and treatment of PFOS-induced hepatic disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China; Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yao
authors.affiliation: Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Xu
authors.affiliation: Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Xian-Ce
authors.initials: XC
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Cheng-Yan
authors.initials: CY
authors.lastname: Geng
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Chuan-Zhou
authors.initials: CZ
authors.lastname: Gao
authors.affiliation: Department of Hygiene, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China.
authors.forename: Lai-Fu
authors.initials: LF
authors.lastname: Zhong
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, 9WLushunSouth Road, Dalian 116044, PR China. Electronic address: yufang_ma@hotmail.com.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Ma
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects*; D005466:Fluorocarbons / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects*; D010539:Permeability
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid
keywords: Autophagy; HepG2 cell; Lysosomal membrane permeabilization; Perfluorooctane sulfonate