title: Tea Polyphenols Protect Against Methylmercury-Induced Cell Injury in Rat Primary Cultured Astrocytes, Involvement of Oxidative Stress and Glutamate Uptake/Metabolism Disorders.
abstract: Methylmercury (MeHg) is an extremely dangerous environmental contaminant, accumulating preferentially in CNS and causing a series of cytotoxic effects. However, the precise mechanisms are still incompletely understood. The current study explored the mechanisms that contribute to MeHg-induced cell injury focusing on the oxidative stress and Glu uptake/metabolism disorders in rat primary cultured astrocytes. Moreover, the neuroprotective effects of tea polyphenols (TP), a natural antioxidant, against MeHg cytotoxicity were also investigated. Astrocytes were exposed to 0, 2.5, 5, 10, and 20 μM MeHgCl for 6-30 h, or pretreated with 50, 100, 200, and 400 μM TP for 1-12 h; cell viability and LDH release were then determined. For further experiments, 50, 100, and 200 μM of TP pretreatment for 6 h followed by 10 μM MeHgCl for 24 h were performed for the examination of the responses of astrocytes, specifically addressing NPSH levels, ROS generation, ATPase activity, the expressions of Nrf2 pathway as well as Glu metabolism enzyme GS and Glu transporters (GLAST and GLT-1). Exposure of MeHg resulted in damages of astrocytes, which were shown by a loss of cell viability, and supported by high levels of LDH release, morphological changes, apoptosis rates, and NPSH depletion. In addition, astrocytes were sensitive to MeHg-mediated oxidative stress, a finding that is consistent with ROS overproduction; Nrf2 as well as its downstream genes HO-1 and γ-GCSh were markedly upregulated. Moreover, MeHg significantly inhibited GS activity, as well as expressions of GS, GLAST, and GLT-1. On the contrary, pretreatment with TP presented a concentration-dependent prevention against MeHg-mediated cytotoxic effects of astrocytes. In conclusion, the findings clearly indicated that MeHg aggravated oxidative stress and Glu uptake/metabolism dysfunction in astrocytes. TP possesses some abilities to prevent MeHg cytotoxicity through its antioxidative properties.
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning province, China. zfxu@mail.cmu.edu.cn.
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning province, China.
authors.forename: Tianyao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning province, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008767:Methylmercury Compounds; D018384:Oxidative Stress / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013662:Tea / Q000737:chemistry; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005721:Glutamate-Cysteine Ligase; D018698:Glutamic Acid; D051547:Heme Oxygenase-1; D007770:L-Lactate Dehydrogenase; D008767:Methylmercury Compounds; D059808:Polyphenols; D017382:Reactive Oxygen Species; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase; D013662:Tea; D051267:NF-E2-Related Factor 2
keywords: Astrocytes; Glutamate metabolism; Glutamate uptake; Methylmercury; Oxidative stress; Tea polyphenols