title: Pinocembrin Suppresses H2O2-Induced Mitochondrial Dysfunction by a Mechanism Dependent on the Nrf2/HO-1 Axis in SH-SY5Y Cells.
abstract: Mitochondria are susceptible to redox impairment, which has been associated with neurodegeneration. These organelles are both a source and target of reactive species. In that context, there is increasing interest in finding natural compounds that modulate mitochondrial function and mitochondria-related signaling in order to prevent or to treat diseases involving mitochondrial impairment. Herein, we investigated whether and how pinocembrin (PB) would prevent mitochondrial dysfunction elicited by the exposure of human neuroblastoma SH-SY5Y cells to hydrogen peroxide (H2O2). PB (25 μM) was administrated for 4 h before H2O2treatment (300 μM for 24 h). PB prevented H2O2-induced loss of cell viability mitochondrial depolarization in SH-SY5Y cells. PB also attenuated redox impairment in mitochondrial membranes. The production of superoxide anion radical (O2-•) and nitric oxide (NO•) was alleviated by PB in cells exposed to H2O2. PB suppressed the H2O2-induced inhibition of the tricarboxylic acid (TCA) cycle enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Furthermore, PB induced anti-inflammatory effects by abolishing the H2O2-dependent activation of the nuclear factor-κB (NF-κB) and upregulation of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The PB-induced antioxidant and anti-inflammatory effects are dependent on the heme oxygenate-1 (HO-1) enzyme and on the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), since HO-1 inhibition (with 0.5 μM ZnPP IX) or Nrf2 silencing (with small interfering RNA (siRNA)) abolished the effects of PB. Overall, PB afforded cytoprotection by the Nrf2/HO-1 axis in H2O2-treated SH-SY5Y cells.
authors.affiliation: Department of Chemistry/ICET, Federal University of Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, Cuiaba, MT, 78060-900, Brazil. mrobioq@gmail.com.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: da Costa Ferreira
authors.affiliation: Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil.
authors.forename: Flávia Bittencourt
authors.initials: FB
authors.lastname: Brasil
authors.affiliation: Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.|Centro de Pesquisa da Pós-Graduação, Centro Universitário Metodista IPA, Porto Alegre, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Peres
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D044950:Flavanones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C016063:pinocembrin; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1
keywords: Mitochondria; NF-κB; Nrf2; Pinocembrin; Respiratory chain; Tricarboxylic aid cycle