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Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP.
Can J Physiol Pharmacol. 2017 Jun; 95(6):750-758.CJ

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+Show Affiliations

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.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.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.c Department of Hematology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28187263

Citation

Zhang, Ruyi, et al. "Tetrahydroxystilbene Glucoside Inhibits Α-synuclein Aggregation and Apoptosis in A53T Α-synuclein-transfected Cells Exposed to MPP." Canadian Journal of Physiology and Pharmacology, vol. 95, no. 6, 2017, pp. 750-758.
Zhang R, Sun F, Zhang L, et al. Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP. Can J Physiol Pharmacol. 2017;95(6):750-758.
Zhang, R., Sun, F., Zhang, L., Sun, X., & Li, L. (2017). Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP. Canadian Journal of Physiology and Pharmacology, 95(6), 750-758. https://doi.org/10.1139/cjpp-2016-0209
Zhang R, et al. Tetrahydroxystilbene Glucoside Inhibits Α-synuclein Aggregation and Apoptosis in A53T Α-synuclein-transfected Cells Exposed to MPP. Can J Physiol Pharmacol. 2017;95(6):750-758. PubMed PMID: 28187263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP. AU - Zhang,Ruyi, AU - Sun,Fangling, AU - Zhang,Lan, AU - Sun,Xuejing, AU - Li,Lin, Y1 - 2017/02/10/ PY - 2017/2/12/pubmed PY - 2018/1/10/medline PY - 2017/2/11/entrez KW - A53T α-synuclein-transfected cell KW - MPP+ KW - Parkinson’s disease KW - cellules transfectées avec le gène de l’α-synucléine portant la mutation A53T KW - maladie de Parkinson KW - tetrahydroxystilbene glucoside KW - tétrahydroxystilbène glucoside KW - α-synuclein KW - α-synucléine SP - 750 EP - 758 JF - Canadian journal of physiology and pharmacology JO - Can J Physiol Pharmacol VL - 95 IS - 6 N2 - 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. SN - 1205-7541 UR - https://www.unboundmedicine.com/medline/citation/28187263/Tetrahydroxystilbene_glucoside_inhibits_α_synuclein_aggregation_and_apoptosis_in_A53T_α_synuclein_transfected_cells_exposed_to_MPP_ L2 - https://cdnsciencepub.com/doi/10.1139/cjpp-2016-0209?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -