Astaxanthin prevents mitochondrial impairment in the dopaminergic SH-SY5Y cell line exposed to glutamate-mediated excitotoxicity: Role for the Nrf2/HO-1/CO-BR axis.

Autor: Brasil FB; Departamento de Ciências da Natureza, Campus Universitário de Rio das Ostras - Universidade Federal Fluminense (UFF), Rio de Janeiro, Brazil., de Almeida FJS; Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Universidade Federal de Mato Grosso (UFMT), Cuiaba, MT, Brazil; Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Departamento de Química, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil., Luckachaki MD; Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Departamento de Química, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil., Dall'Oglio EL; Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Departamento de Química, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil., de Oliveira MR; Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Departamento de Química, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil. Electronic address: mrobioq@gmail.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2021 Oct 05; Vol. 908, pp. 174336. Date of Electronic Publication: 2021 Jul 13.
DOI: 10.1016/j.ejphar.2021.174336
Abstrakt: Mitochondrial dysfunction has been viewed in several diseases, including neurological disorders. In the glutamate (GLU)-mediated excitotoxicity, it has been described mitochondrial impairment, disrupted redox environment, and increased rates of cell death in the affected brain areas. Astaxanthin (AST) is a potent antioxidant and anti-inflammatory xanthophyll that also promotes beneficial mitochondria-related effects in brain cells. However, it is not completely clear how AST would be able to promote mitochondrial protection in those cell types. Thus, we investigated here how AST would protect mitochondria in the dopaminergic SH-SY5Y cell line exposed to GLU. AST was administrated to the cells at 1-40 μM for 24 h prior to the exposure to GLU at 80 mM for additional 24 h. AST prevented the GLU-induced impairment in the activity of the Complexes I and V, the loss in mitochondrial membrane potential (MMP), and the decline in the synthesis of ATP. AST also induced an antioxidant effect in the membranes of mitochondria obtained from the GLU-treated SH-SY5Y cells. Inhibition of the enzyme heme oxygenase-1 (HO-1) or silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) suppressed the AST-promoted cellular and mitochondrial protection. Either tricarbonyldichlororuthenium(II) dimer (CORM-2, a source of carbon monoxide - CO) or bilirubin (BR), that are products of the HO-1-biliverdin reductase (BVR) axis, blocked some of the effects caused by GLU in the SH-SY5Y cells. Overall, our data demonstrate that AST prevented mitochondrial dysfunction by a mechanism related to the Nrf2/HO-1 axis in GLU-challenged cells.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: