title: Tanshinone I Attenuates the Effects of a Challenge with H2O2on the Functions of Tricarboxylic Acid Cycle and Respiratory Chain in SH-SY5Y Cells.
abstract: Tanshinone I (T-I; C18H12O3) is a cytoprotective molecule. T-I has been viewed as an antioxidant and anti-inflammatory agent exerting neuroprotective actions in several experimental models. Nonetheless, the mechanisms underlying the beneficial effects of T-I in mammalian cells are not completely understood yet. Mitochondrial dysfunction has been associated with several neurodegenerative diseases which remain uncured. Therefore, there is increasing interest in compounds that may be used in the prevention or treatment of those pathologies. Since T-I presents an antioxidant capacity, we investigated here whether and how this compound would prevent mitochondrial impairment in SH-SY5Y cells exposed to hydrogen peroxide (H2O2), which has been involved in the triggering of deleterious effects in several experimental models mimicking neurodegenerative processes. We found that a pretreatment with T-I at 2.5 μM for 2 h suppressed the pro-oxidant effects of H2O2on mitochondrial membranes. Furthermore, T-I prevented the H2O2-elicited inhibition of the tricarboxylic acid (TCA) cycle enzymes (aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase) and of the mitochondrial complexes I and V. T-I also abrogated the mitochondrial depolarization and the mitochondrial failure to produce ATP in cells exposed to H2O2. T-I upregulated the levels of reduced glutathione (GSH) in the mitochondria of SH-SY5Y cells. T-I induced mitochondrial protection, at least in part, by activating the nuclear factor erythroid 2-related factor 2 (Nrf2), because silencing of Nrf2 by using small interference RNA (SiRNA) blocked these effects. Therefore, T-I afforded mitochondrial protection (involving both redox and bioenergetics-related aspects) against H2O2through the activation of Nrf2.
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, Cuiabá, MT, CEP 78060-900, Brazil. mrobioq@gmail.com.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Instituto de Genética e Bioquímica (INGEB), Universidade Federal de Uberlândia (UFU), Patos de Minas, MG, Brazil.
authors.forename: Cristina Ribas
authors.initials: CR
authors.lastname: Fürstenau
authors.affiliation: Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBIO), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Instituto de Biologia, Universidade Federal de Pelotas (UFPel), Pelotas, RS, Brazil.
authors.forename: Izabel Cristina Custódio
authors.initials: ICC
authors.lastname: de Souza
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: da Costa Ferreira
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C021751:tanshinone; D006861:Hydrogen Peroxide; D005978:Glutathione
keywords: Antioxidant; Mitochondria; Nrf2; Tanshinone I; Tricarboxylic acid cycle