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Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels

Author

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  • Chisato Kinoshita

    (Teikyo University School of Medicine)

  • Koji Aoyama

    (Teikyo University School of Medicine)

  • Nobuko Matsumura

    (Teikyo University School of Medicine)

  • Kazue Kikuchi-Utsumi

    (Teikyo University School of Medicine)

  • Masahiko Watabe

    (Teikyo University School of Medicine
    General Medical Education Center (G-MEC), Teikyo University School of Medicine)

  • Toshio Nakaki

    (Teikyo University School of Medicine)

Abstract

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.

Suggested Citation

  • Chisato Kinoshita & Koji Aoyama & Nobuko Matsumura & Kazue Kikuchi-Utsumi & Masahiko Watabe & Toshio Nakaki, 2014. "Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4823
    DOI: 10.1038/ncomms4823
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    Cited by:

    1. Catherine Mooney & Rana Raoof & Hany El-Naggar & Amaya Sanz-Rodriguez & Eva M Jimenez-Mateos & David C Henshall, 2015. "High Throughput qPCR Expression Profiling of Circulating MicroRNAs Reveals Minimal Sex- and Sample Timing-Related Variation in Plasma of Healthy Volunteers," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-20, December.

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