title: BPA-toxicity via superoxide anion overload and a deficit in β-catenin signaling in human bone mesenchymal stem cells.
abstract: Bisphenol A (BPA), used in the manufacture of products based on polycarbonate plastics and epoxy resins, is well known as an endocrine-disrupting monomer. In the current study, BPA increased cytotoxicity in hBMSCs in a dose- and time-dependent manner, concomitantly with increased lipid peroxidation. Increased cell death in BPA-treated cells was markedly blocked by pretreatment with the superoxide dismutase mimetic MnTBAP and MnTMPyP, but not by catalase, glutathione, the glutathione peroxidase mimetic ebselen, the NOS inhibitor NAME, or the xanthine oxidase inhibitor allopurinol. Furthermore, the decline in nuclear β-catenin and cyclin D1 levels in hBMSCs exposed to BPA was reversed by MnTBAP treatment. Finally, treatment of hBMSCs with the GSK3β inhibitor LiCl2increased nuclear β-catenin levels and significantly attenuated cytotoxicity compared with BPA treatment. Our current results in hBMSCs exposed to BPA suggest that BPA causes a disturbance in β-catenin signaling via a superoxide anion overload. © 2016 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc. Environ Toxicol 32: 344-352, 2017.
authors.affiliation: Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University, Seoul, 158-710, Republic of Korea.
authors.forename: Yea-Hyun
authors.initials: YH
authors.lastname: Leem
authors.affiliation: Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University, Seoul, 158-710, Republic of Korea.
authors.forename: Seikwan
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Hong-Je
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul, 138-736, Republic of Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul, 138-736, Republic of Korea.
authors.forename: Juno
authors.initials: J
authors.lastname: Yoon
authors.affiliation: Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul, 138-736, Republic of Korea.
authors.forename: Jae-Suk
authors.initials: JS
authors.lastname: Chang
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018021:Lithium Chloride / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D000493:Allopurinol; D000975:Antioxidants; D001559:Benzhydryl Compounds; D002374:Catalase; D019938:Cyclin D1; D005978:Glutathione; D005979:Glutathione Peroxidase; D018021:Lithium Chloride; D010636:Phenols; D013482:Superoxide Dismutase; D013481:Superoxides; D051176:beta Catenin; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: GSK3β; MnTBAP; bisphenol A; human bone mesenchymal stem cells; superoxide dismutase; β-catenin
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