Astaxanthin Counteracts Excitotoxicity and Reduces the Ensuing Increases in Calcium Levels and Mitochondrial Reactive Oxygen Species Generation
Francisca García,
Pedro Lobos,
Alejandra Ponce,
Karla Cataldo,
Daniela Meza,
Patricio Farías,
Carolina Estay,
Felipe Oyarzun-Ampuero,
Rodrigo Herrera-Molina,
Andrea Paula-Lima,
Álvaro O. Ardiles,
Cecilia Hidalgo,
Tatiana Adasme,
Pablo Muñoz
Affiliations
Francisca García
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Pedro Lobos
Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile
Alejandra Ponce
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Karla Cataldo
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Daniela Meza
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Patricio Farías
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Carolina Estay
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Felipe Oyarzun-Ampuero
Department of Technology and Pharmaceutical Sciences, Faculty of Chemical and Pharmaceutical Sciences, Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, Independencia, Santiago 8380494, Chile
Rodrigo Herrera-Molina
Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany
Andrea Paula-Lima
Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile
Álvaro O. Ardiles
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Cecilia Hidalgo
Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile
Tatiana Adasme
Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O’Higgins, Santiago 8370854, Chile
Pablo Muñoz
Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca2+ concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca2+ 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 Ca2+ sensor, ASX also prevented the increase in intracellular Ca2+ concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca2+ increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca2+ homeostasis and ROS generation.