Promotion of Mitochondrial Protection by Emodin in Methylglyoxal-Treated Human Neuroblastoma SH-SY5Y Cells: Involvement
- PDF / 735,942 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 56 Downloads / 177 Views
ORIGINAL ARTICLE
Promotion of Mitochondrial Protection by Emodin in Methylglyoxal-Treated Human Neuroblastoma SH-SY5Y Cells: Involvement of the AMPK/Nrf2/HO-1 Axis Marcos Roberto de Oliveira 1
&
Izabel Cristina Custódio de Souza 2 & Flávia Bittencourt Brasil 3
Received: 1 August 2020 / Revised: 7 September 2020 / Accepted: 8 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Mitochondrial dysfunction is part of the mechanism of several human diseases. This negative circumstance may be induced by certain toxicants, as methylglyoxal (MG). MG is a reactive dicarbonyl presenting both endogenous and exogenous sources and is also able to induce protein cross-linking and glycation. Emodin (EM; 1,3,8-trihydroxy-6methylanthracene-9,10-dione; C15H10O5) is a cytoprotective agent. Nonetheless, it was not previously demonstrated whether EM would be able to promote mitochondrial protection in cells challenged with MG. Therefore, we investigated here whether and how EM would prevent the MG-induced mitochondrial collapse in the human neuroblastoma SH-SY5Y cells. We found that a pretreatment (for 4 h) with EM at 40 μM prevented the MG-induced mitochondrial dysfunction (i.e., decreased activity of the complexes I and V, reduced adenosine triphosphate levels, and loss of mitochondrial membrane potential) in the SH-SY5Y cells. EM also prevented the redox impairment induced by MG in mitochondrial membranes. Inhibiting the adenosine monophosphate-activated protein kinase (AMPK) or silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2), transcription factor abolished the EM-induced protection. Inhibition of heme oxygenase-1 (HO-1) also blocked the EM-induced mitochondrial protection. Therefore, EM protected the mitochondria by a mechanism dependent on the AMPK/Nrf2/HO-1 signaling pathway in MGchallenged SH-SY5Y cells. Keywords Emodin . Antioxidant . SH-SY5Y cells . Methylglyoxal . Mitochondria . Bioenergetics
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12640-020-00287-w) contains supplementary material, which is available to authorized users. * Marcos Roberto de Oliveira [email protected]; [email protected] 1
Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP, Cuiaba, MT 78060-900, Brazil
2
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
3
Departamento de Ciências da Natureza, Campus Universitário de Rio das Ostras – Universidade Federal Fluminense (UFF), Rio de Janeiro, Brazil
The reactive dicarbonyl methylglyoxal (MG) is a toxicant originated from both endogenous (e.g., sugar glycolysis, catabolism of glycine and threonine, acetone metabolism) and exogenous (e.g., degradation of toluene, sucrose caramelization, others) sources and is
Data Loading...
