title: The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2nanoparticles to human endothelial cells.
abstract: It was recently shown that ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress in human umbilical vein endothelial cells (HUVECs). If ER stress is associated the toxicity of ZnO NPs, the presence of ER stress inducer thapsigargin (TG) should alter the response of HUVECs to ZnO NP exposure. In this study, we addressed this issue by assessing cytotoxicity, oxidative stress and inflammatory responses in ZnO NP exposed HUVECs with or without the presence of TG. Moreover, TiO2NPs were used to compare the effects. Exposure to 32 μg/mL ZnO NPs (p < 0.05), but not TiO2NPs (p > 0.05), significantly induced cytotoxicity as assessed by WST-1 and neutral red uptake assay, as well as intracellular ROS. ZnO NPs dose-dependently increased the accumulation of intracellular Zn ions, and ZnSO4induced similar cytotoxic effects as ZnO NPs, which indicated a role of Zn ions. The release of inflammatory proteins tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) or the adhesion of THP-1 monocytes to HUVECs was not significantly affected by ZnO or TiO2NP exposure (p > 0.05). The presence of 250 nM TG significantly induced cytotoxicity, release of IL-6 and THP-1 monocyte adhesion (p < 0.01), but did not significantly affect intracellular ROS or release of TNFα (p > 0.05). ANOVA analysis indicated no interaction between exposure to ZnO NPs and the presence of TG on almost all the endpoints (p > 0.05) except neutral red uptake assay (p < 0.01). We concluded ER stress is probably not associated with ZnO NP exposure induced oxidative stress and inflammatory responses in HUVECs.
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Gui
authors.initials: G
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Shen
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Xiyue
authors.initials: X
authors.lastname: Li
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties; D019284:Thapsigargin / Q000737:chemistry / Q000633:toxicity*; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D019284:Thapsigargin; D014025:Titanium; D015034:Zinc Oxide
keywords: TiO2 nanoparticles; ZnO nanoparticles; endoplasmic reticulum stress; human umbilical vein endothelial cells; thapsigargin