PMID- 27997269 OWN - NLM STAT- MEDLINE DCOM- 20170726 LR - 20220331 IS - 1537-6524 (Electronic) IS - 1537-6516 (Linking) VI - 27 IP - 3 DP - 2017 Mar TI - The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO(2) nanoparticles to human endothelial cells. PG - 191-200 LID - 10.1080/15376516.2016.1273429 [doi] AB - 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, TiO(2) NPs were used to compare the effects. Exposure to 32 mug/mL ZnO NPs (p < 0.05), but not TiO(2) 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 ZnSO(4) induced similar cytotoxic effects as ZnO NPs, which indicated a role of Zn ions. The release of inflammatory proteins tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) or the adhesion of THP-1 monocytes to HUVECs was not significantly affected by ZnO or TiO(2) 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 TNFalpha (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. FAU - Gu, Yuxiu AU - Gu Y AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Cheng, Shanshan AU - Cheng S AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Chen, Gui AU - Chen G AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Shen, Yuexin AU - Shen Y AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Li, Xiyue AU - Li X AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Jiang, Qin AU - Jiang Q AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Li, Juan AU - Li J AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. FAU - Cao, Yi AU - Cao Y AD - a Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry , College of Chemistry, Xiangtan University , Xiangtan , PR China. LA - eng PT - Journal Article DEP - 20170108 PL - England TA - Toxicol Mech Methods JT - Toxicology mechanisms and methods JID - 101134521 RN - 0 (Reactive Oxygen Species) RN - 15FIX9V2JP (titanium dioxide) RN - 67526-95-8 (Thapsigargin) RN - D1JT611TNE (Titanium) RN - SOI2LOH54Z (Zinc Oxide) SB - IM MH - Cell Line MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Endoplasmic Reticulum Stress/*drug effects MH - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism/ultrastructure MH - Humans MH - Nanoparticles/chemistry/*toxicity MH - Oxidative Stress/drug effects MH - Particle Size MH - Reactive Oxygen Species/metabolism MH - Surface Properties MH - Thapsigargin/chemistry/*toxicity MH - Titanium/chemistry/*toxicity MH - Zinc Oxide/chemistry/*toxicity OTO - NOTNLM OT - TiO2 nanoparticles OT - ZnO nanoparticles OT - endoplasmic reticulum stress OT - human umbilical vein endothelial cells OT - thapsigargin EDAT- 2016/12/21 06:00 MHDA- 2017/07/27 06:00 CRDT- 2016/12/21 06:00 PHST- 2016/12/21 06:00 [pubmed] PHST- 2017/07/27 06:00 [medline] PHST- 2016/12/21 06:00 [entrez] AID - 10.1080/15376516.2016.1273429 [doi] PST - ppublish SO - Toxicol Mech Methods. 2017 Mar;27(3):191-200. doi: 10.1080/15376516.2016.1273429. Epub 2017 Jan 8.