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Inhibition of the Nrf2/HO-1 Axis Suppresses the Mitochondria-Related Protection Promoted by Gastrodin in Human Neuroblastoma Cells Exposed to Paraquat

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Abstract

Mitochondria are double-membrane organelles involved in the transduction of energy from different metabolic substrates into adenosine triphosphate (ATP) in mammalian cells. The oxidative phosphorylation system is comprised by the activity of the respiratory chain and the complex V (ATP synthase/ATPase). This system is dependent on oxygen gas (O2) in order to maintain a flux of electrons in the respiratory chain, since O2 is the final acceptor of these electrons. Electron leakage from this complex system leads to the continuous generation of reactive species in the cells. The mammalian cells exhibit certain mechanisms to attenuate the consequences originated from the constant exposure to these reactive species. In this context, the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and one of the enzymes whose expression is modulated by Nrf2, heme oxygenase-1 (HO-1), take a central role in inducing cytoprotection in humans. Mitochondrial abnormalities are observed during intoxication and in certain diseases, including neurodegeneration. Mitochondrial protection promoted by natural compounds has attracted the attention of researchers due to the promising effects these agents induce experimentally. In this regard, we examined here whether and how gastrodin (GAS), a phenolic glucoside, would prevent the paraquat (PQ)-induced mitochondrial impairment in the SH-SY5Y cells. The cells were exposed to GAS (25 μM) for 4 h prior to the challenge with PQ at 100 μM for additional 24 h. The silencing of Nrf2 by siRNA or the inhibition of HO-1 by ZnPP IX suppressed the GAS-elicited cytoprotection. Therefore, GAS promoted mitochondrial protection by an Nrf2/HO-1-dependent manner.

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Acknowledgements

This work was supported by CNPq (Universal 2016).

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Authors and Affiliations

  1. Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, Cuiaba, MT, 78060-900, Brazil

    Marcos Roberto de Oliveira

  2. Programa de Pós-Graduação em Química (PPGQ), Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil

    Marcos Roberto de Oliveira

  3. Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil

    Marcos Roberto de Oliveira

  4. Departamento de Ciências da Natureza, Campus Universitário de Rio das Ostras, Universidade Federal Fluminense (UFF), Rio de Janeiro, Brazil

    Flávia de Bittencourt Brasil

  5. Instituto de Biotecnologia (IBTEC), Universidade Federal de Uberlândia (UFU), Patos de Minas, MG, Brazil

    Cristina Ribas Fürstenau

Authors
  1. Marcos Roberto de Oliveira
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  2. Flávia de Bittencourt Brasil
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  3. Cristina Ribas Fürstenau
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Correspondence to Marcos Roberto de Oliveira.

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Figure S1

The effects of gastrodin on the levels of nuclear Nrf2 (A) and total heme oxygenase-1 (HO-1) (B) in SH-SY5Y cells. The cells were exposed to gastrodin at 25 μM for 0–24 h, depending on the parameter analyzed. Data are shown as the mean ± SEM of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, * p < 0.05 different from the control group. (PDF 83 kb)

Figure S2

The effect of Nrf2 silencing by siRNA (48 h) on the levels of heme oxygenase-1 (HO-1) in gastrodin-treated SH-SY5Y cells. The cells were exposed to gastrodin at 25 μM for 24 h. Data are shown as the mean ± SEM of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 different from the control group, ** p < 0.05 different from the gastrodin-treated cells transfected with negative control (NC) siRNA.. (PDF 5 kb)

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de Oliveira, M.R., de Bittencourt Brasil, F. & Fürstenau, C.R. Inhibition of the Nrf2/HO-1 Axis Suppresses the Mitochondria-Related Protection Promoted by Gastrodin in Human Neuroblastoma Cells Exposed to Paraquat. Mol Neurobiol 56, 2174–2184 (2019). https://doi.org/10.1007/s12035-018-1222-6

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  • DOI: https://doi.org/10.1007/s12035-018-1222-6

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