Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes

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Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes

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作者：Fang Yuntao ; Guo Chenjia ; Zhang Panpan ; Zhao Wenjun ; Wang Suhua…
关键词：Methylmercury ; Autophagy ; Neurotoxicity ; Antioxidants ; Neuroprotection ; Astrocytes
刊名：Archives of Toxicology
出版年：2016
出版时间：February 2016
年：2016
卷：90
期：2
页码：333-345
全文大小：3,425 KB
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作者单位：Fang Yuntao (1)
Guo Chenjia (1)
Zhang Panpan (1)
Zhao Wenjun (1)
Wang Suhua (1)
Xing Guangwei (1)
Shi Haifeng (2)
Lu Jian (1)
Peng Wanxin (3)
Feng Yun (4)
Jiyang Cai (5)
Michael Aschner (6)
Lu Rongzhu (1)

1. Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
2. Institute of Life Sciences, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
3. Department of Biology, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
4. Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
5. Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX, 77550-1106, USA
6. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
刊物主题：Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine general;
出版者：Springer Berlin Heidelberg
ISSN：1432-0738

文摘

Autophagy is an evolutionarily conserved process in which cytoplasmic proteins and organelles are degraded and recycled for reuse. There are numerous reports on the role of autophagy in cell growth and death; however, the role of autophagy in methylmercury (MeHg)-induced neurotoxicity has yet to be identified. We studied the role of autophagy in MeHg-induced neurotoxicity in astrocytes. MeHg reduced astrocytic viability in a concentration- and time-dependent manner, and induced apoptosis. Pharmacological inhibition of autophagy with 3-methyladenine or chloroquine, as well as the silencing of the autophagy-related protein 5, increased MeHg-induced cytotoxicity and the ratio of apoptotic astrocytes. Conversely, rapamycin, an autophagy inducer, along with as N-acetyl-l-cysteine, a precursor of reduced glutathione, decreased MeHg-induced toxicity and the ratio of apoptotic astrocytes. These results indicated that MeHg-induced neurotoxicity was reduced, at least in part, through the activation of autophagy. Accordingly, modulation of autophagy may offer a new avenue for attenuating MeHg-induced neurotoxicity. Keywords Methylmercury Autophagy Neurotoxicity Antioxidants Neuroprotection Astrocytes