机构地区:[1]Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China [3]Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, China [4]the Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China
出 处:《中国药理学与毒理学杂志》2017年第10期1004-1004,共1页Chinese Journal of Pharmacology and Toxicology
摘 要:Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.
关 键 词:dimethyl sulfide Parkinson disease methionine sulfoxidereductase A 6-HYDROXYDOPAMINE
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