title: Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP.
abstract: Increasing evidence has solidified the involvement of α-synuclein (α-Syn) and neurotoxins in the pathogenesis of Parkinson's disease (PD), suggesting a combination of genetic and environmental influences. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on α-Syn aggregation, mitochondrial dysfunction, oxidative stress, and apoptosis in vitro. A53T mutant α-synuclein-transfected cells (A53T AS cells) plus MPP+exposure were used as a complex cell model of PD. The expression of proteins was determined by Western blot assay. Flow cytometry was utilized to measure mitochondrial membrane potential and apoptosis. The results showed that MPP+exposure for 24 h induced more severe damage in A53T AS cells than in vector control cells. Pretreatment of TSG for 24 h significantly increased the cell viability; decreased lactate dehydrogenase leakage; inhibited α-Syn over-expression and aggregation; elevated mitochondrial membrane potential; decreased reactive oxygen species, Bax/Bcl-2 ratio, and caspase-3 activity; and inhibited apoptosis in A53T AS cells exposed to MPP+. These results suggest that TSG may be an attractive candidate for PD therapy.
authors.affiliation: a Department of Pharmacology, Xuanwu Hospital of Capital Medical University; Beijing Geriatric Medical Research Center; Beijing Institute for Brain Disorders; Beijing Engineering Research Center for Nerve System Drugs; Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacology, Xuanwu Hospital of Capital Medical University; Beijing Geriatric Medical Research Center; Beijing Institute for Brain Disorders; Beijing Engineering Research Center for Nerve System Drugs; Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.|b Experimental Animal Laboratory, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
authors.forename: Fangling
authors.initials: F
authors.lastname: Sun
authors.affiliation: a Department of Pharmacology, Xuanwu Hospital of Capital Medical University; Beijing Geriatric Medical Research Center; Beijing Institute for Brain Disorders; Beijing Engineering Research Center for Nerve System Drugs; Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: c Department of Hematology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Sun
authors.affiliation: a Department of Pharmacology, Xuanwu Hospital of Capital Medical University; Beijing Geriatric Medical Research Center; Beijing Institute for Brain Disorders; Beijing Engineering Research Center for Nerve System Drugs; Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D066329:Protein Aggregates / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D005960:Glucosides; D066329:Protein Aggregates; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051844:alpha-Synuclein; D051028:bcl-2-Associated X Protein; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium
keywords: A53T α-synuclein-transfected cell; MPP+; Parkinson’s disease; cellules transfectées avec le gène de l’α-synucléine portant la mutation A53T; maladie de Parkinson; tetrahydroxystilbene glucoside; tétrahydroxystilbène glucoside; α-synuclein; α-synucléine