Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels.
Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels.
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DOI：
10.1038/ncomms4823
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发表时间：
2014-05-07
影响因子：
16.6
通讯作者：
Nakaki, Toshio
中科院分区：
文献类型：
--
作者：
Kinoshita, Chisato;Aoyama, Koji;Matsumura, Nobuko;Kikuchi-Utsumi, Kazue;Watabe, Masahiko;Nakaki, Toshio
谷胱甘肽（GSH）是一种重要的抗氧化剂，在大脑中起着重要的神经保护作用。GSH水平降低与神经退行性疾病如帕金森病和阿尔茨海默病有关。在这里，我们表明，谷胱甘肽水平的昼夜波动与多巴胺能细胞对氧化应激的神经保护活性。此外，我们发现参与神经元GSH合成的半胱氨酸转运蛋白兴奋性氨基酸载体1（EAAC 1）受到microRNA miR-96- 5 p的负调控，表现出昼夜节律。通过脑室内给予抑制剂阻断miR-96- 5 p可增加EAAC 1和GSH的水平，并对小鼠黑质中的氧化应激具有神经保护作用。我们的研究结果表明，miR-96- 5 p的昼夜节律可能通过EAAC 1调节神经元GSH水平在神经保护中发挥作用。 谷氨酸是一种关键的抗氧化剂，在大脑中起着重要的神经保护作用。Kinoshita等人发现，谷胱甘肽的水平表现出昼夜波动，这是由microRNA miR-96- 5 p间接调节的，并且这种microRNA对氧化应激起着神经保护作用。
Glutathione (GSH) is a key antioxidant that plays an important neuroprotective role in the brain. Decreased GSH levels are associated with neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Here we show that a diurnal fluctuation of GSH levels is correlated with neuroprotective activity against oxidative stress in dopaminergic cells. In addition, we found that the cysteine transporter excitatory amino acid carrier 1 (EAAC1), which is involved in neuronal GSH synthesis, is negatively regulated by the microRNA miR-96-5p, which exhibits a diurnal rhythm. Blocking miR-96-5p by intracerebroventricular administration of an inhibitor increased the level of EAAC1 as well as that of GSH and had a neuroprotective effect against oxidative stress in the mouse substantia nigra. Our results suggest that the diurnal rhythm of miR-96-5p may play a role in neuroprotection by regulating neuronal GSH levels via EAAC1. Glutathione is a key antioxidant that plays an important neuroprotective role in the brain. Here, Kinoshita et al. show that levels of glutathione exhibit diurnal fluctuations that are indirectly regulated by the microRNA miR-96-5p, and that this microRNA plays a neuroprotective role against oxidative stress.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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