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

Francisca García,Cecilia Hidalgo,Felipe Oyarzun-Ampuero,Pablo Muñoz,Rodrigo Herrera-Molina,Karla Cataldo,Tatiana Adasme,Patricio Farías,Álvaro O Ardiles,Pedro Lobos,Daniela Meza,Alejandra Ponce,Carolina Estay,Andrea Paula-Lima

doi:10.3390/md18060335

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-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.

Highlights

Astaxanthin (ASX) is an orange-red carotenoid pigment produced by the microalgaeHaematococcus pluvialis, the red yeast Phaffia rhodozyma and other marine species [1]
We found that ASX decreased mitochondrial reactive oxygen species (ROS) levels and alleviated the mitochondrial dysfunction induced in SH-SY5Y cells by NMDA and prevented H2 O2 -induced cell death
SH-SY5Y cells, a human neuroblastoma cell line derived from the catecholaminergic line

Summary

Introduction

Astaxanthin (ASX) is an orange-red carotenoid pigment produced by the microalgae. Haematococcus pluvialis, the red yeast Phaffia rhodozyma and other marine species [1]. Due to its strong anti-oxidant properties, ASX has been considered as a promising molecule for the treatment of inflammation, cancer, and age-related diseases [2,3,4]. In neuron-like HT22 cells [7], PC12 cells [8] or SH-SY5Y cells [9,10,11] ASX suppresses the excitotoxic responses induced by glutamate, 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) or acetaldehyde. The neuroprotective effects of ASX might involve decreasing oxidative stress and improving mitochondrial integrity [12], whether ASX induces adaptive responses such as changes in redox-sensitive cellular signaling processes-including calcium (Ca2+ )-dependent signaling pathways and reactive oxygen species (ROS) generation remains largely unknown.

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Conclusion