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Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin induced apoptosis in SH-SY5Y cells.
Environ Toxicol. 2016 Sep; 31(9):1068-79.ET

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+Show Affiliations

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.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.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.Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001, China.Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001, China.Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, China.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25865073

Citation

Zhao, Jianmei, et al. "Autophagy Potentially Protects Against 2,3,7,8-tetrachlorodibenzo-p-Dioxin Induced Apoptosis in SH-SY5Y Cells." Environmental Toxicology, vol. 31, no. 9, 2016, pp. 1068-79.
Zhao J, Tang C, Nie X, et al. Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin induced apoptosis in SH-SY5Y cells. Environ Toxicol. 2016;31(9):1068-79.
Zhao, J., Tang, C., Nie, X., Xi, H., Jiang, S., Jiang, J., Liu, S., Liu, X., Liang, L., Wan, C., & Yang, J. (2016). Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin induced apoptosis in SH-SY5Y cells. Environmental Toxicology, 31(9), 1068-79. https://doi.org/10.1002/tox.22116
Zhao J, et al. Autophagy Potentially Protects Against 2,3,7,8-tetrachlorodibenzo-p-Dioxin Induced Apoptosis in SH-SY5Y Cells. Environ Toxicol. 2016;31(9):1068-79. PubMed PMID: 25865073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin induced apoptosis in SH-SY5Y cells. AU - Zhao,Jianmei, AU - Tang,Cuiying, AU - Nie,Xiaoke, AU - Xi,Hanqing, AU - Jiang,Shengyang, AU - Jiang,Junkang, AU - Liu,Suyi, AU - Liu,Xipeng, AU - Liang,Lingwei, AU - Wan,Chunhua, AU - Yang,Jianbin, Y1 - 2015/04/10/ PY - 2014/09/16/received PY - 2014/12/30/revised PY - 2015/01/01/accepted PY - 2015/4/14/entrez PY - 2015/4/14/pubmed PY - 2017/3/9/medline KW - SH-SY5Y cells KW - TCDD KW - apoptosis KW - autophagy KW - reactive oxygen species (ROS) SP - 1068 EP - 79 JF - Environmental toxicology JO - Environ Toxicol VL - 31 IS - 9 N2 - 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. SN - 1522-7278 UR - https://www.unboundmedicine.com/medline/citation/25865073/Autophagy_potentially_protects_against_2378_tetrachlorodibenzo_p_Dioxin_induced_apoptosis_in_SH_SY5Y_cells_ L2 - https://doi.org/10.1002/tox.22116 DB - PRIME DP - Unbound Medicine ER -