title: Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells.
abstract: Nanomaterials are used in diverse fields including food, cosmetic, and medical industries. Titanium dioxide nanoparticles (TiO2-NP) are widely used, but their effects on biological systems and mechanism of toxicity have not been elucidated fully. Here, we report the toxicological mechanism of TiO2-NP in cell organelles. Human bronchial epithelial cells (16HBE14o-) were exposed to 50 and 100 μg/mL TiO2-NP for 24 and 48 h. Our results showed that TiO2-NP induced endoplasmic reticulum (ER) stress in the cells and disrupted the mitochondria-associated endoplasmic reticulum membranes (MAMs) and calcium ion balance, thereby increasing autophagy. In contrast, an inhibitor of ER stress, tauroursodeoxycholic acid (TUDCA), mitigated the cellular toxic response, suggesting that TiO2-NP promoted toxicity via ER stress. This novel mechanism of TiO2-NP toxicity in human bronchial epithelial cells suggests that further exhaustive research on the harmful effects of these nanoparticles in relevant organisms is needed for their safe application.
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul, Korea.
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul, Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.affiliation: R&D Center, Biterials Co., Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Chemistry, College of Natural Sciences, Gwanak-gu, Seoul National University, Seoul, Korea.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Chemistry, College of Natural Sciences, Gwanak-gu, Seoul National University, Seoul, Korea.
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Applied Bioscience, College of Life Science, CHA University, Pocheon-shi, Gyeonggi-do, Korea.
authors.forename: Tae-Jong
authors.initials: TJ
authors.lastname: Yoon
authors.affiliation: R&D Center, Biterials Co., Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea, Korea.
authors.forename: Jun-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul, Korea; Graduate Group of Tumor Biology, Seoul National University, Gwanak-gu, Seoul, Korea; Graduate School of Convergence Science and Technology, Seoul National University, Yeongtong-Gu, Suwon, Gyeonggi-Do, Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon, Gyeonggi-Do, Korea.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008168:Lung / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D014025:Titanium / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014025:Titanium; D002118:Calcium