title: Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes.
abstract: 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.
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuntao
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chenjia
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Panpan
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wenjun
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Suhua
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Guangwei
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Haifeng
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jian
authors.affiliation: Department of Biology, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wanxin
authors.affiliation: Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yun
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX, 77550-1106, USA.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Department of Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China. lurz@mail.ujs.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Rongzhu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002738:Chloroquine / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008767:Methylmercury Compounds / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology*; D051381:Rats
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008767:Methylmercury Compounds; D002738:Chloroquine; D000111:Acetylcysteine
keywords: Antioxidants; Astrocytes; Autophagy; Methylmercury; Neuroprotection; Neurotoxicity