Dimethyl sulfide,a metabolite of the marine microorganism,protects SH-SY5Y cells against 6-hydroxydopamine and MPP+-induced apoptosis

Peng-fei WU,Xin-lei GUAN,Han LUO,Fang WANG,3,4,Jian-Guo CHEN,3,4

(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)

T2-27

Dimethyl sulfide,a metabolite of the marine microorganism,protects SH-SY5Y cells against 6-hydroxydopamine and MPP+-induced apoptosis

Peng-fei WU1,2,3,4,Xin-lei GUAN1,Han LUO1,Fang WANG1,3,4,Jian-Guo CHEN1,3,4

(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)

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 cytopro⁃tection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,MsrA 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;Parkinson disease;methionine sulfoxidereductase A;6-hydroxydopamine