title: The antioxidant ESeroS-GS inhibits NO production and prevents oxidative stress in astrocytes.
abstract: Within the central nervous system uncontrolled production of large amounts of nitric oxide (NO) by activated glial cells might be the common pathogenesis of several neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. In the present investigation, we measured the effect of a novel antioxidant gamma-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-cysteinyl-glycine sodium salt (ESeroS-GS) on NO production in cultured rat astrocytes. Upon stimulation with 1 microg/mL lipopolysaccharide plus 100 U/mL interferon-gamma which induced the expression of inducible nitric oxide synthase, cultured astrocytes generated large amounts of NO as measured by nitrite assay and ESR technique. The endogenous NO caused oxidative damage in astrocytes, which was confirmed by the accumulation of both cytosolic and extracellular peroxides, the decrease in the cellular glutathione level, and the formation of thiobarbituric acid reactive substrates. Production of endogenous NO resulted in cell death finally. Pretreatment with the novel antioxidant ESeroS-GS effectively decreased the expression of iNOS gene, inhibited the formation of endogenous NO, and prevented NO-induced oxidative damage and cell death in astrocytes. The results suggest that ESeroS-GS might be used as a potential agent for the prevention and therapy of diseases associated with the overproduction of NO by activated astrocytes.
authors.affiliation: Center for Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, PR China. weitt@moon.ibp.ac.cn
authors.forename: Taotao
authors.initials: T
authors.lastname: Wei
authors.forename: Xingyu
authors.initials: X
authors.lastname: Zhao
authors.forename: Jingwu
authors.initials: J
authors.lastname: Hou
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ogata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sakaue
authors.forename: Akitane
authors.initials: A
authors.lastname: Mori
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D016923:Cell Death; D002478:Cells, Cultured; D003600:Cytosol; D005978:Glutathione / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects*; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D007211:Indoles; D008070:Lipopolysaccharides; D010545:Peroxides; 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; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D001205:Ascorbic Acid