Astaxanthin Counteracts Excitotoxicity and Reduces the Ensuing Increases in Calcium Levels and Mitochondrial Reactive Oxygen Species Generation

Garcia, Francisca; Lobos, Pedro; Ponce, Alejandra; Cataldo, Karla; Meza, Daniela; Farias, Patricio; Estay, Carolina; Oyarzun-Ampuero, Felipe; Herrera-Molina, Rodrigo; Paula-Lima, Andrea; Ardiles, Alvaro O.; Hidalgo, Cecilia; Adasme, Tatiana; Munoz, Pablo

Abstract

Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-beta peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca(2+)concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca(2+)dysregulation. Here, we studied whether ASX protects neurons from N-methyl-D-aspartate (NMDA)-induced excitotoxicity, a noxious process which decreases cellular viability, alters gene expression and promotes excessive mROS production. Incubation of the neuronal cell line SH-SY5Y with NMDA decreased cellular viability and increased mitochondrial superoxide production; pre-incubation with ASX prevented these effects. Additionally, incubation of SH-SY5Y cells with ASX effectively reduced the basal mROS production and prevented hydrogen peroxide-induced cell death. In primary hippocampal neurons, transfected with a genetically encoded cytoplasmic Ca(2+)sensor, ASX also prevented the increase in intracellular Ca(2+)concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca(2+)increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca(2+)homeostasis and ROS generation.

Más información

Título según WOS: ID WOS:000551180900003 Not found in local WOS DB
Título de la Revista: MARINE DRUGS
Volumen: 18
Número: 6
Editorial: MDPI
Fecha de publicación: 2020
DOI:

10.3390/md18060335

Notas: ISI