title: Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin induced apoptosis in SH-SY5Y cells.
abstract: The environmental toxicant TCDD may elicit cytotoxic effects by inducing reactive oxygen species (ROS) generation. Autophagy is one of the first lines of defense against oxidative stress damage. Herein, we investigated whether autophagy played a regulatory role in TCDD-induced neurotoxicity. Here, we showed that TCDD exposure caused marked autophagy in SH-SY5Y cells, whose dose range was close to that inducing apoptosis. Electron microscopic and Western blot analyses revealed that TCDD induced autophagy at a starting dose of approximate 100 nM. Interestingly, 100-200 nM TCDD exposure resulted in obviously decreased cell viability and evident apoptotic phenotype. Furthermore, the levels of pro-apoptotic molecules, Bax and cleaved-PARP, increased significantly, whereas Bcl2 declined after exposed to 100 nM TCDD. In addition, the apoptosis was verified using flow cytometrical analysis. These data strongly suggested that TCDD induced both autophagy and apoptosis at a similar dose range in SH-SY5Y cells. Interestingly, pretreatment with ROS scavenger, N-acetyl-cysteine (NAC), could effectively block both TCDD-induced apoptosis and autophagy. More surprisingly, inhibition of autophagy with 3-methyladenine (3MA), remarkably augmented TCDD-induced apoptosis. The findings implicated that the onset of autophagy might serve as a protective mechanism to ameliorate ROS-triggered cytotoxic effects in human SH-SY5Y neuronal cells under TCDD exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1068-1079, 2016.
authors: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.|Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Jianmei
authors: J
authors: Zhao
authors: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Cuiying
authors: C
authors: Tang
authors: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.|Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Xiaoke
authors: X
authors: Nie
authors: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
authors: Hanqing
authors: H
authors: Xi
authors: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Shengyang
authors: S
authors: Jiang
authors: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Junkang
authors: J
authors: Jiang
authors: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Suyi
authors: S
authors: Liu
authors: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Xipeng
authors: X
authors: Liu
authors: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.
authors: Lingwei
authors: L
authors: Liang
authors: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Chunhua
authors: C
authors: Wan
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.|Department of Disease Prevention, Second People's Hospital of Nantong, Nantong University, Nantong, Jiangsu Province, 226001, China.
authors: Jianbin
authors: J
authors: Yang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C025946:3-methyladenine; D000225:Adenine; D000111:Acetylcysteine
keywords: SH-SY5Y cells; TCDD; apoptosis; autophagy; reactive oxygen species (ROS)