PMID- 31325888 OWN - NLM STAT- MEDLINE DCOM- 20191107 LR - 20211204 IS - 1873-6424 (Electronic) IS - 0269-7491 (Linking) VI - 253 DP - 2019 Oct TI - BDE-209 induces autophagy and apoptosis via IRE1alpha/Akt/mTOR signaling pathway in human umbilical vein endothelial cells. PG - 429-438 LID - S0269-7491(19)30850-4 [pii] LID - 10.1016/j.envpol.2019.07.030 [doi] AB - Recently, the essentiality and fatalness of cardiovascular diseases is attracting much attention. Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants, which could induce the toxic effect and have been implicated in the occurrence and development of cardiovascular diseases. However, it is unclear how autophagy and apoptosis induced by BDE-209 in endothelial cells are regulated. The aim of the present study was to investigate the effects of BDE-209 on human umbilical vein endothelial cells (HUVECs) and elucidate the mechanisms involved. HUVECs were treated with a wide range concentration of BDE-209 for 24 h. The appearance of autophagy was tested by the testing index such as outcomes of monodansylcadaverine (MDC) staining and lysotracker staining, observation of autophagosomes and conversion between autophagy marker light chain 3 (LC3)-I and LC3-II. Besides, the apoptotic cell rate was detected with flow cytometry. In addition, BDE-209 induced endoplasmic reticulum (ER) stress was detected by transmission electron microscopy (TEM). Our data suggest that the exposure of BDE-209 could induce autophagy, which was confirmed by MDC staining, transmission electron microscopy observation, lysotracker staining and LC3-I/LC3-II conversion. Besides, the ER stress-related inositol-requiring enzyme 1alpha (IRE1alpha)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway could be activated by reactive oxygen species (ROS) to regulate autophagy. Moreover, the apoptosis of endothelial cells was alleviated when autophagy was blocked by 3-Methyladenine (3-MA). The results demonstrated that BDE-209 could induce the production of ROS and ER stress, activate autophagy through IRE1alpha/AKT/mTOR signaling pathway and ultimately induce apoptosis of vascular endothelial cells. These findings indicate that exposure to PBDE is possible to be a potential risk factor for cardiovascular diseases. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Hou, Yun AU - Hou Y AD - Department of Histology and Embryology, Binzhou Medical University, Yantai, PR China. FAU - Fu, Jiarong AU - Fu J AD - College of Clinical Medicine, Bin Zhou Medical University, Yan Tai, PR China. FAU - Sun, Shitian AU - Sun S AD - College of Clinical Medicine, Bin Zhou Medical University, Yan Tai, PR China. FAU - Jin, Yinchuan AU - Jin Y AD - Department of Histology and Embryology, Binzhou Medical University, Yantai, PR China. FAU - Wang, Xifeng AU - Wang X AD - Department of Critical Care Medicine, Yu Huang Ding Hospital, Qingdao University, Yantai, PR China. FAU - Zhang, Lianshuang AU - Zhang L AD - Department of Histology and Embryology, Binzhou Medical University, Yantai, PR China. Electronic address: zls197600@126.com. LA - eng PT - Journal Article DEP - 20190710 PL - England TA - Environ Pollut JT - Environmental pollution (Barking, Essex : 1987) JID - 8804476 RN - 0 (Environmental Pollutants) RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Reactive Oxygen Species) RN - 4L6452S749 (Inositol) RN - 7REL09ZX35 (pentabromodiphenyl ether) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.- (Endoribonucleases) RN - N80BQ29A0H (decabromobiphenyl ether) SB - IM MH - Apoptosis/drug effects MH - Autophagy/drug effects MH - Endoplasmic Reticulum Stress/drug effects MH - Endoribonucleases MH - Environmental Pollutants/*toxicity MH - Halogenated Diphenyl Ethers/*toxicity MH - Human Umbilical Vein Endothelial Cells/drug effects MH - Humans MH - Inositol MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/metabolism MH - Toxicity Tests MH - Umbilical Veins EDAT- 2019/07/22 06:00 MHDA- 2019/11/08 06:00 CRDT- 2019/07/21 06:00 PHST- 2019/02/17 00:00 [received] PHST- 2019/05/22 00:00 [revised] PHST- 2019/07/06 00:00 [accepted] PHST- 2019/07/22 06:00 [pubmed] PHST- 2019/11/08 06:00 [medline] PHST- 2019/07/21 06:00 [entrez] AID - S0269-7491(19)30850-4 [pii] AID - 10.1016/j.envpol.2019.07.030 [doi] PST - ppublish SO - Environ Pollut. 2019 Oct;253:429-438. doi: 10.1016/j.envpol.2019.07.030. Epub 2019 Jul 10.