title: Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial pathway in human hepatic cells: a proteomic study.
abstract: Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated compounds, and exposure to it has been associated with a number of adverse health effects. However, the molecular mechanisms involved in PFOA toxicity are still not well characterized. In the present study, flow cytometry analysis revealed that PFOA induced oxidative stress, cell cycle arrest and apoptosis in human non-tumor hepatic cells (L-02). Furthermore, we investigated the alterations in protein profile within L-02 cells exposed to PFOA, aiming to explore the mechanisms underlying PFOA hepatotoxicity on the proteome level. Of the 28 proteins showing significant differential expression in response to PFOA, 24 were down-regulated and 4 were up-regulated. This proteomic study proposed that the inhibition of some proteins, including GRP78, HSP27, CTSD and hnRNPC may be involved in the activation of p53, which consequently triggered the apoptotic process in L-02 cells. Induction of apoptosis via the p53-dependent mitochondrial pathway is further suggested as one of the key toxicological events occurring in L-02 cells under PFOA stress. We hope these data will shed new light on the molecular mechanisms responsible for PFOA-mediated toxicity in human liver cells, and from such studies useful biomarkers indicative of PFOA exposure could be developed.
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Francis L
authors.initials: FL
authors.lastname: Martin
authors.forename: Siyuan
authors.initials: S
authors.lastname: Peng
authors.forename: Meiping
authors.initials: M
authors.lastname: Tian
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Mu
authors.forename: Heqing
authors.initials: H
authors.lastname: Shen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002210:Caprylates / Q000633:toxicity*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D000091342:Endoplasmic Reticulum Chaperone BiP; D005466:Fluorocarbons / Q000633:toxicity*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D002210:Caprylates; D000091342:Endoplasmic Reticulum Chaperone BiP; D005466:Fluorocarbons; C000717247:HSPA5 protein, human; D020543:Proteome; D016159:Tumor Suppressor Protein p53; C023036:perfluorooctanoic acid
keywords: Apoptosis; Human hepatic cells; Mitochondrial pathway; Perfluorooctanoic acid; Proteomics; p53