Neurochemical Research

, Volume 41, Issue 1–2, pp 5–15 | Cite as

Upregulation of Slc38a1 Gene Along with Promotion of Neurosphere Growth and Subsequent Neuronal Specification in Undifferentiated Neural Progenitor Cells Exposed to Theanine

  • Takeshi Takarada
  • Masato Ogura
  • Noritaka Nakamichi
  • Takami Kakuda
  • Ryota Nakazato
  • Hiroshi Kokubo
  • Shinsuke Ikeno
  • Saki Nakamura
  • Takaya Kutsukake
  • Eiichi Hinoi
  • Yukio Yoneda
Original Paper


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.


Theanine Glutamine transporter SLC38A1 Neural progenitors Neurosphere Neuronal specification 



Activator protein-1


Activating transcription factor-2


Activating transcription factor-2


Activating transcription factor-3


All-trans retinoic acid


Basic helix-loop-helix




Constitutive active activating transcription factor-6


Constitutive active hypoxia inducible factor-1α


CCAAT enhancer binding protein-α


Ciliary neurotrophic factor


Ciliary neurotrophic factor receptor alpha


Cyclic AMP responsive element binding protein


Dulbecco’s modified Eagle medium: Nutrient Mixture F-12


Endoplasmic reticulum


Empty vector


Fetal bovine serum


Fibroblast growth factor


Glyceraldehyde-3-phosphate dehydrogenase


Glial fibrillary acidic protein




Hypoxia inducible factor-1α


Microtubules-associated protein-2


3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide


Neural cell adhesion molecule


Nuclear factor of activated T cell-1


Nuclear factor-κB


Nuclear factor (erythroid-derived 2)-like 2




Phosphate-buffered saline


Polymerase chain reaction


Retinoic acid receptor alpha


Reverse transcription polymerase chain reaction


Solute carrier 38a1


Signal transducer and activator of transcription-1


Signal transducer and activator of transcription-3




X-box binding protein-1



This work was in part supported by Grants-in-Aids for Scientific Research to TT (No. 22500330) and YY (Nos. 18053009 and 24650196) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Takeshi Takarada
    • 1
  • Masato Ogura
    • 1
    • 3
  • Noritaka Nakamichi
    • 1
    • 4
  • Takami Kakuda
    • 2
  • Ryota Nakazato
    • 1
  • Hiroshi Kokubo
    • 1
  • Shinsuke Ikeno
    • 1
  • Saki Nakamura
    • 1
  • Takaya Kutsukake
    • 1
  • Eiichi Hinoi
    • 1
  • Yukio Yoneda
    • 1
  1. 1.Laboratory of Molecular Pharmacology, Division of Pharmaceutical SciencesKanazawa University Graduate School of Medical, Pharmaceutical and Health SciencesKakuma-machi, KanazawaJapan
  2. 2.Research Center of Composite MaterialFukuoka UniversityFukuokaJapan
  3. 3.Department of Biomolecular ScienceFukushima Medical University School of MedicineFukushimaJapan
  4. 4.Laboratory of Molecular PharmacotherapeuticsKanazawa University Graduate SchoolKanazawaJapan

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