title: Zinc oxide nanoparticle induced autophagic cell death and mitochondrial damage via reactive oxygen species generation.
abstract: Zinc oxide nanoparticles (ZnO-np) are used in an increasing number of industrial products such as paint, coating and cosmetics, and in other biological applications. There have been many suggestions of a ZnO-np toxicity paradigm but the underlying molecular mechanisms about the toxicity of ZnO-np remain unclear. This study was done to determine the potential toxicity of ZnO-np and to assess the toxicity mechanism in normal skin cells. Synthesized ZnO-np generated reactive oxygen species (ROS), as determined by electron spin resonance. After uptake into cells, ZnO-np induced ROS in a concentration- and time-dependent manner. To demonstrate ZnO-np toxicity mechanism related to ROS, we detected abnormal autophagic vacuoles accumulation and mitochondria dysfunction after ZnO-np treatment. Furthermore mitochondria membrane potential and adenosine-5'-triphosphate (ATP) production are decreased for culture with ZnO-np. We conclude that ZnO-np leads to cell death through autophagic vacuole accumulation and mitochondria damage in normal skin cells via ROS induction. Accordingly, ZnO-np may cause toxicity and the results highlight and need for careful regulation of ZnO-np production and use.
authors: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Kyeong-Nam
authors: KN
authors: Yu
authors: Tae-Jong
authors: TJ
authors: Yoon
authors: Arash
authors: A
authors: Minai-Tehrani
authors: Ji-Eun
authors: JE
authors: Kim
authors: Soo Jin
authors: SJ
authors: Park
authors: Min Sook
authors: MS
authors: Jeong
authors: Shin-Woo
authors: SW
authors: Ha
authors: Jin-Kyu
authors: JK
authors: Lee
authors: Jun Sung
authors: JS
authors: Kim
authors: Myung-Haing
authors: MH
authors: Cho
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D015034:Zinc Oxide