Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile.
Translational Neurology Center, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile.
Mar Drugs. 2020 Jun 26;18(6):335. doi: 10.3390/md18060335.
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 Ca concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca 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 sensor, ASX also prevented the increase in intracellular Ca concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca homeostasis and ROS generation.
虾青素（ASX）是一种具有强大抗氧化性能的类胡萝卜素色素。我们之前曾报道过，ASX 可保护神经元免受淀粉样β肽寡聚物的有害影响，淀粉样β肽寡聚物可促进过多的线粒体活性氧（mROS）产生，并诱导细胞质 Ca 浓度持续增加。这些特性使 ASX 成为一种有前途的治疗剂，可用于治疗涉及氧化和 Ca 失调的病理状况。在这里，我们研究了 ASX 是否可保护神经元免受 N-甲基-D-天冬氨酸（NMDA）诱导的兴奋性毒性的侵害，这种有害过程会降低细胞活力，改变基因表达并促进过多的 mROS 产生。用 NMDA 孵育神经元细胞系 SH-SY5Y 会降低细胞活力并增加线粒体超氧化物的产生；用 ASX 预先孵育可防止这些作用。此外，用 ASX 孵育 SH-SY5Y 细胞可有效降低基础 mROS 产生并防止过氧化氢诱导的细胞死亡。在用遗传编码的细胞质 Ca 传感器转染的原代海马神经元中，ASX 还可防止 NMDA 诱导的细胞内 Ca 浓度增加。我们认为，通过防止兴奋性毒性条件下发生的有害 mROS 和 Ca 增加，ASX 可作为涉及 Ca 动态平衡和 ROS 产生改变的神经退行性病变的治疗剂。
