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The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells.
Toxicol Mech Methods. 2017 Mar; 27(3):191-200.TM

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, TiO2 NPs were used to compare the effects. Exposure to 32 μg/mL ZnO NPs (p < 0.05), but not TiO2 NPs (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 ZnSO4 induced 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 TiO2 NP 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.

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Authors+Show Affiliations

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China.

MeSH

Cell LineCell SurvivalDose-Response Relationship, DrugEndoplasmic Reticulum StressHuman Umbilical Vein Endothelial CellsHumansNanoparticlesOxidative StressParticle SizeReactive Oxygen SpeciesSurface PropertiesThapsigarginTitaniumZinc Oxide

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27997269

Citation

Gu, Yuxiu, et al. "The Effects of Endoplasmic Reticulum Stress Inducer Thapsigargin On the Toxicity of ZnO or TiO2 Nanoparticles to Human Endothelial Cells." Toxicology Mechanisms and Methods, vol. 27, no. 3, 2017, pp. 191-200.

Gu Y, Cheng S, Chen G, et al. The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells. Toxicol Mech Methods. 2017;27(3):191-200.

Gu, Y., Cheng, S., Chen, G., Shen, Y., Li, X., Jiang, Q., Li, J., & Cao, Y. (2017). The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells. Toxicology Mechanisms and Methods, 27(3), 191-200. https://doi.org/10.1080/15376516.2016.1273429

Gu Y, et al. The Effects of Endoplasmic Reticulum Stress Inducer Thapsigargin On the Toxicity of ZnO or TiO2 Nanoparticles to Human Endothelial Cells. Toxicol Mech Methods. 2017;27(3):191-200. PubMed PMID: 27997269.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells. AU - Gu,Yuxiu, AU - Cheng,Shanshan, AU - Chen,Gui, AU - Shen,Yuexin, AU - Li,Xiyue, AU - Jiang,Qin, AU - Li,Juan, AU - Cao,Yi, Y1 - 2017/01/08/ PY - 2016/12/21/pubmed PY - 2017/7/27/medline PY - 2016/12/21/entrez KW - TiO2 nanoparticles KW - ZnO nanoparticles KW - endoplasmic reticulum stress KW - human umbilical vein endothelial cells KW - thapsigargin SP - 191 EP - 200 JF - Toxicology mechanisms and methods JO - Toxicol Mech Methods VL - 27 IS - 3 N2 - 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, TiO2 NPs were used to compare the effects. Exposure to 32 μg/mL ZnO NPs (p < 0.05), but not TiO2 NPs (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 ZnSO4 induced 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 TiO2 NP 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. SN - 1537-6524 UR - https://www.unboundmedicine.com/medline/citation/27997269/The_effects_of_endoplasmic_reticulum_stress_inducer_thapsigargin_on_the_toxicity_of_ZnO_or_TiO2_nanoparticles_to_human_endothelial_cells_ DB - PRIME DP - Unbound Medicine ER -