title: Upregulation of Slc38a1 Gene Along with Promotion of Neurosphere Growth and Subsequent Neuronal Specification in Undifferentiated Neural Progenitor Cells Exposed to Theanine.
abstract: We have shown marked promotion of both cluster growth and neuronal specification in pluripotent P19 cells with overexpression of solute carrier 38a1 (Slc38a1), which is responsible for membrane transport of glutamine. In this study, we evaluated pharmacological profiles of the green tea amino acid ingredient theanine, which is a good substrate for glutamine transporters, on proliferation and neuronal specification in neural progenitor cells from embryonic rat neocortex. Sustained exposure to theanine, but not glutamine, accelerated the growth of neurospheres composed of proliferating cells and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reducing activity at concentrations of 1-100 μM in undifferentiated progenitor cells. Such prior exposure to theanine promoted spontaneous and induced commitment to a neuronal lineage with concomitant deteriorated astroglial specification. Selective upregulation was seen in the expression of Slc38a1 in progenitor cells cultured with theanine. Similarly significant increases in cluster growth and MTT reducing activity were found in P19 cells cultured with theanine for 4 days. Luciferase activity was doubled in a manner sensitive to the deletion of promoter regions in P19 cells with a luciferase reporter plasmid of the Slc38a1 promoter after sustained exposure to theanine for 4 days. Overexpression of X-box binding protein-1 led to a marked increase in luciferase activity in P19 cells transfected with the Slc38a1 reporter plasmid. These results suggest that theanine accelerates cellular proliferation and subsequent neuronal specification through a mechanism relevant to upregulation of Slc38a1 gene in undifferentiated neural progenitor cells.
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takarada
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.|Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.|Laboratory of Molecular Pharmacotherapeutics, Kanazawa University Graduate School, Kanazawa, 920-1192, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Nakamichi
authors.affiliation: Research Center of Composite Material, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Kakuda
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Nakazato
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kokubo
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ikeno
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Kutsukake
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hinoi
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan. yyoneda@p.kanazawa-u.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D026924:Amino Acid Transport System A / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D005971:Glutamates / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D026924:Amino Acid Transport System A; D005971:Glutamates; D012333:RNA, Messenger; C432411:Slc38a1 protein, mouse; C486716:Slc38a1 protein, rat; C026166:theanine
keywords: Glutamine transporter; Neural progenitors; Neuronal specification; Neurosphere; SLC38A1; Theanine