title: Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels.
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.
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Kinoshita
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Aoyama
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Kikuchi-Utsumi
authors.affiliation: 1] Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan [2] General Medical Education Center (G-MEC), Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watabe
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D002460:Cell Line; D002940:Circadian Rhythm; D059290:Dopaminergic Neurons / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000096:biosynthesis / Q000235:genetics*; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D018384:Oxidative Stress; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D000975:Antioxidants; D050580:Excitatory Amino Acid Transporter 3; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D018696:Neuroprotective Agents; C493400:SLC1A1 protein, human; D005978:Glutathione