title: Tanshinone I Induces Mitochondrial Protection through an Nrf2-Dependent Mechanism in Paraquat-TreatedHuman Neuroblastoma SH-SY5Y Cells.
abstract: Tanshinone I (T-I; 1,6-Dimethylnaphtho[1,2-g][1]benzofuran-10,11-dione; C18H12O3), which may be found in Salvia miltiorrhiza Bunge (Danshen), is a potent anti-inflammatory, antioxidant, and anti-cancer agent. At least in part, T-I exerts antioxidant activity by activating signaling pathways associated with the maintenance of the redox state in mammalian cells. In this context, the upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has received attention regarding the role of this transcription factor in modulating the expression of antioxidant enzymes and the metabolism of glutathione (GSH). Even though there is a growing body of evidence suggesting that T-I mediates protection against several pro-oxidant challenges in both in vitro and in vivo experimental models, it remains to be examined whether and how T-I would modulate mitochondrial function during redox disturbances. Therefore, we aimed to reveal whether T-I would exhibit protective effects on mitochondria of SH-SY5Y cells treated with paraquat (PQ), a well-known mitochondrial toxic agent. We found that T-I pretreatment significantly protected mitochondria against PQ-induced redox impairment through an Nrf2-dependent mechanism involving upregulation of antioxidant enzymes, such as Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and both catalytic and modifier subunits of γ-glutamate-cysteine ligase (γ-GCL). T-I prevented complex I and mitochondrial membrane potential (MMP) impairments elicited by PQ. Thus, T-I may be viewed as a new mitochondrial protective agent whose complete mechanism of action needs to be investigated, but it seems to involve mitochondriotropic aspects related to the chemistry of this molecule.
authors.affiliation: Programa de Pós-Graduação em Química, Departamento de Química (DQ), Instituto de Ciências Exatas e da Terra (ICET), Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP, Cuiabá, MT, 78060-900, Brazil. mrobioq@gmail.com.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), Programa de Pós-Graduação em Ciências da Saúde, Criciúma, SC, Brazil.
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
authors.forename: Simone Morelo Dal
authors.initials: SMD
authors.lastname: Bosco
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010269:Paraquat / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000378:metabolism; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C021751:tanshinone; D042967:Electron Transport Complex I; D005978:Glutathione; D010269:Paraquat
keywords: Antioxidant; Mitochondria; Nrf2; Paraquat; Tanshinone I