title: SWCNTs induced autophagic cell death in human bronchial epithelial cells.
abstract: Carbon nanotubes are being actively introduced in electronics, computer science, aerospace, and other industries. Thus, the urgent need for toxicological studies on CNTs is mounting. In this study, we investigated the alterations in cellular response with morphological changes induced by single-walled carbon nanotubes (SWCNTs) in BEAS-2B cells, a human bronchial epithelial cell line. At 24h after exposure, SWCNTs rapidly decreased ATP production and cell viability as well a slight increase in the number of cells in the subG1 and G1 phases. In addition, SWCNTs increased the expression of superoxide dismutase (SOD)-1, but not SOD-2, and the number of cells generating ROS. The concentration of Cu and Zn ions also increased in a dose-dependent manner in cells exposed to SWCNTs. SWCNTs significantly enhanced the release of nitric oxide, interleukin (IL)-6, and IL-8 and up-regulated the expression of chemokine- and cytokine-related genes. Furthermore, the levels of autophagy-related genes, especially the DRAM1 gene, and the autophagosome formation-related proteins, were clearly up-regulated together with an increase of autophagosome-like vacuoles. Based on these results, we suggest that SWCNTs induce autophagic cell death through mitochondrial dysfunction and cytosolic damage in human bronchial epithelial cells.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: world1@ajou.ac.kr.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Nur Elida M
authors.initials: NE
authors.lastname: Zahari
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Eun-Woo
authors.initials: EW
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jaewhan
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Jae-Hyeok
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: jhkim@ajou.ac.kr.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D003600:Cytosol / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D037742:Nanotubes, Carbon; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human
keywords: Autophagy; DRAM1; Mitochondria; SWCNT; Starvation