title: Titanium dioxide nanoparticles alter cellular morphology via disturbing the microtubule dynamics.
abstract: Titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in our daily lives, for example, in the areas of sunscreens, cosmetics, toothpastes, food products, and nanomedical reagents. Recently, increasing concern has been raised about their neurotoxicity, but the mechanisms underlying such toxic effects are still unknown. In this work, we employed a human neuroblastoma cell line (SH-SY5Y) to study the effects of TiO2 NPs on neurological systems. Our results showed that TiO2 NPs did not affect cell viability but induced noticeable morphological changes until 100 μg ml(-1). Immunofluorescence detection showed disorder, disruption, retraction, and decreased intensity of the microtubules after TiO2 NPs treatment. Both α and β tubule expressions did not change in the TiO2 NP-treated group, but the percentage of soluble tubules was increased. A microtubule dynamic study in living cells indicated that TiO2 NPs caused a lower growth rate and a higher shortening rate of microtubules as well as shortened lifetimes of de novo microtubules. TiO2 NPs did not cause changes in the expression and phosphorylation state of tau proteins, but a tau-TiO2 NP interaction was observed. TiO2 NPs could interact with tubule heterodimers, microtubules and tau proteins, which led to the instability of microtubules, thus contributing to the neurotoxicity of TiO2 NPs.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211100, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Mao
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ji
authors.forename: Kun
authors.initials: K
authors.lastname: Zhou
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.forename: Xiumei
authors.initials: X
authors.lastname: Han
authors.forename: Qiusha
authors.initials: Q
authors.lastname: Tang
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000633:toxicity*; D008870:Microtubules / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D014025:Titanium