PMID- 28171821
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20171128
IS  - 1872-7077 (Electronic)
IS  - 1382-6689 (Linking)
VI  - 50
DP  - 2017 Mar
TI  - The endoplasmic reticulum stress inducer thapsigargin enhances the toxicity of 
      ZnO nanoparticles to macrophages and macrophage-endothelial co-culture.
PG  - 103-110
LID - S1382-6689(17)30027-3 [pii]
LID - 10.1016/j.etap.2017.01.020 [doi]
AB  - It was recently shown that exposure to ZnO nanoparticles (NPs) could induce 
      endoplasmic reticulum (ER) stress both in vivo and in vitro, but the role of ER 
      stress in ZnO NP induced toxicity remains unclear. Because macrophages are 
      sensitive to ER stress, we hypothesized that stressing macrophages with ER stress 
      inducer could enhance the toxicity of ZnO NPs. In this study, the effects of ER 
      stress inducer thapsigargin (TG) on the toxicity of ZnO NPs to THP-1 macrophages 
      were investigated. The results showed that TG enhanced ZnO NP induced 
      cytotoxicity as revealed by water soluble tetrazolium-1 (WST-1) and neutral red 
      uptake assays, but not lactate dehydrogenase (LDH) assay. ZnO NPs 
      dose-dependently enhanced the accumulation of intracellular Zn ions without the 
      induction of reactive oxygen species (ROS), and the presence of TG did not 
      significantly affect these effects. In the co-culture, exposure of THP-1 
      macrophages in the upper chamber to ZnO NPs and TG significantly reduced the 
      viability of human umbilical vein endothelial cells (HUVECs) in the lower 
      chamber, but the release of tumor necrosis factor alpha (TNFalpha) was not induced. In 
      summary, our data showed that stressing THP-1 macrophages with TG enhanced the 
      cytotoxicity of ZnO NPs to macrophages and macrophage-endothelial co-cultures.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Chen, Gui
AU  - Chen G
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China.
FAU - Shen, Yuexin
AU  - Shen Y
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China.
FAU - Li, Xiyue
AU  - Li X
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China.
FAU - Jiang, Qin
AU  - Jiang Q
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China.
FAU - Cheng, Shanshan
AU  - Cheng S
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China.
FAU - Gu, Yuxiu
AU  - Gu Y
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China.
FAU - Liu, Liangliang
AU  - Liu L
AD  - Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 
      410205, PR China. Electronic address: liuliangliang@caas.cn.
FAU - Cao, Yi
AU  - Cao Y
AD  - Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of 
      Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, 
      Xiangtan 411105, PR China. Electronic address: caoyi39@xtu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170130
PL  - Netherlands
TA  - Environ Toxicol Pharmacol
JT  - Environmental toxicology and pharmacology
JID - 9612020
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67526-95-8 (Thapsigargin)
RN  - SOI2LOH54Z (Zinc Oxide)
SB  - IM
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Coculture Techniques
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Endothelial Cells/*cytology/drug effects
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Macrophages/*cytology/drug effects
MH  - Nanoparticles/toxicity
MH  - Thapsigargin/*pharmacology
MH  - Toxicity Tests
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Zinc Oxide/*toxicity
OTO - NOTNLM
OT  - Co-culture
OT  - Human umbilical vein endothelial cells (HUVECs)
OT  - THP-1 macrophages
OT  - Thapsigargin (TG)
OT  - ZnO nanoparticles (NPs)
EDAT- 2017/02/09 06:00
MHDA- 2017/03/14 06:00
CRDT- 2017/02/08 06:00
PHST- 2016/11/21 00:00 [received]
PHST- 2017/01/22 00:00 [revised]
PHST- 2017/01/26 00:00 [accepted]
PHST- 2017/02/09 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
PHST- 2017/02/08 06:00 [entrez]
AID - S1382-6689(17)30027-3 [pii]
AID - 10.1016/j.etap.2017.01.020 [doi]
PST - ppublish
SO  - Environ Toxicol Pharmacol. 2017 Mar;50:103-110. doi: 10.1016/j.etap.2017.01.020. 
      Epub 2017 Jan 30.