Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice
Joint Authors
Xu, Zhao-Fa
Yang, Xinxin
Wu, Fengdi
Qi, Zhipeng
Li, Jiashuo
Xu, Bin
Liu, Wei
Yang, Hai-Bo
Deng, Yu
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-08-30
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure.
Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity.
It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure.
However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure.
The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo.
Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT.
Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks.
Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured.
Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT.
Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner.
Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present.
In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.
American Psychological Association (APA)
Yang, Xinxin& Yang, Hai-Bo& Wu, Fengdi& Qi, Zhipeng& Li, Jiashuo& Xu, Bin…[et al.]. 2018. Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1211400
Modern Language Association (MLA)
Yang, Xinxin…[et al.]. Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-15.
https://search.emarefa.net/detail/BIM-1211400
American Medical Association (AMA)
Yang, Xinxin& Yang, Hai-Bo& Wu, Fengdi& Qi, Zhipeng& Li, Jiashuo& Xu, Bin…[et al.]. Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1211400
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211400