title: Protective effect of 3H-1, 2-dithiole-3-thione on cellular model of Alzheimer's disease involves Nrf2/ARE signaling pathway.
abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator for a battery of genes encoding detoxifying and antioxidative enzymes. 3H-1, 2-dithiole-3-thione (D3T), a potent free radical scavenger, is able to activate Nrf2 signaling pathway. In the present study, N2a/APPswe cells were used as the Alzheimer's disease (AD) cellular model and we investigated the protective effect of D3T on N2a/APPswe cells and the potential mechanisms. Our assays demonstrated that D3T was able to attenuate reactive oxygen species generation, increase MMP level as well as decrease MDA content. Furthermore, treatment of the cells with 40μM D3T for 24h, showed significant suppression of Aβ level in N2a/APPswe cells. The current study also found that D3T significantly upregulated the Nrf2 mRNA level and protein expression, and subsequently enhanced mRNA expression of HO-1 and NQO1 in N2a/APPswe cells. Meanwhile, down-regulation of Nrf2 by small interference RNA abolished cytoprotection of D3T. Taken together, these results demonstrate that D3T provides neuroprotection in vitro model and therefore may be a potential complement for AD therapy.
authors.affiliation: Department of Neurology, Puai Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430033, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Puai Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430033, China; Department of Neurology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430022, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurology, Huaihe Hospital, Henan University, Kaifeng 47500, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neurology, Puai Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430033, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430022, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430022, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurology, Puai Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430033, China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430022, China.
authors.forename: Curimbacus M
authors.initials: CM
authors.lastname: Afzal
authors.affiliation: Department of Pharmacology, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430022, China. Electronic address: gangli2008@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000235:genetics; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D058990:Molecular Targeted Therapy; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013871:Thiones / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D010446:Peptide Fragments; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013871:Thiones; D013876:Thiophenes; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D005978:Glutathione; C049325:1,2-dithiol-3-thione
keywords: 3H-1, 2-dithiole-3-thione; Alzheimer's disease; N2a/APPswe; Nrf2