NDLI: Tea Polyphenols Protect Against Methylmercury-Induced Cell Injury in Rat Primary Cultured Astrocytes, Involvement of Oxidative Stress and Glutamate Uptake/Metabolism Disorders

Content Provider	Springer Nature Link
Author	Liu, Wei Xu, Zhaofa Yang, Tianyao Deng, Yu Xu, Bin Feng, Shu
Copyright Year	2015
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.
Starting Page	2995
Ending Page	3009
Page Count	15
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	5
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-05-08
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Methylmercury Astrocytes Oxidative stress Glutamate uptake Glutamate metabolism Tea polyphenols Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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