title: ESeroS-GS Protects Neuronal Cells from Oxidative Stress by Stabilizing Lysosomes.
abstract: γ-l-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-l-cysteinylglycine sodium salt (ESeroS-GS) is a water-soluble derivative of α-tocopherol (vitamin E). We reported previously that ESeroS-GS can act as an anti-inflammatory agent and can induce cell death in breast cancer cells. However, the potential antioxidant capacities of ESeroS-GS remain elusive. Here, we measured its scavenging effects on free radicals and evaluated its protective effects on neuronal cells against oxidative stress. The results indicated that ESeroS-GS effectively scavenged both 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonate free radicals (ABTS(•+)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and attenuated H₂O₂-induced neuronal cell death. H₂O₂ treatment induced lysosomal membrane permeabilization rapidly, and caused the redistribution of lysosomal proteases, which were responsible for the neuronal cell death. ESeroS-GS abolished the interaction between tBid and the lysosomal membranes, blocked the translocation of tBid to the lysosomal membranes, decreased its oligomerization within the membrane circumstances, prevented the lysosomal membrane permeabilization, and thus attenuated the neuronal cell death. These data suggest that ESeroS-GS protected the neuronal cells from oxidative stress by stabilizing lysosomal membranes, and thus might act as a novel neuroprotector for neuronal diseases associated with oxidative stress.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. nayang2007@126.com.|University of Chinese Academy of Sciences, Beijing 100049, China. nayang2007@126.com.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. chenqian0621@163.com.|University of Chinese Academy of Sciences, Beijing 100049, China. chenqian0621@163.com.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. xiaolonghe@yeah.net.|University of Chinese Academy of Sciences, Beijing 100049, China. xiaolonghe@yeah.net.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: He
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. pkuibpzxy@gmail.com.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. weitt@moon.ibp.ac.cn.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wei
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D052160:Benzothiazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007211:Indoles / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010851:Picrates / Q000494:pharmacology; D013451:Sulfonic Acids / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D052160:Benzothiazoles; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D007211:Indoles; D010851:Picrates; D013451:Sulfonic Acids; C475739:glutamyl-(2-(((3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl)oxy)carbonyl)-3-((2-(1H-indol-3-yl)ethyl)amino)-3-oxopropyl)-cysteinyl-glycine sodium salt; D014810:Vitamin E; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Bid; ESeroS-GS; antioxidant; cell death; lysosome; neuronal cell; oxidative stress