Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6

Tomohiro Nishimura, Kei Higuchi, Yuko Yoshida, Yuki Sugita-Fujisawa, Kazuaki Kojima, Maiko Sugimoto, Marie Santo, Masatoshi Tomi, Emi Nakashima

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Hypotaurine is a precursor of taurine and a physiological antioxidant that circulates in adult and fetal plasma. The purpose of the present study was to clarify whether hypotaurine is a substrate of Slc6a/gammaaminobutyric acid (GABA) transporter family members. Radiolabeled hypotaurine was synthesized from radiolabeled cysteamine and 2-aminoethanethiol dioxygenase. The uptakes of [3H]GABA, [3H]taurine, and [14C]hypotaurine by HEK293 cells expressing mouse GAT1/Slc6a1, TAUT/Slc6a6, GAT3/Slc6a11, BGT1/ Slc6a12, and GAT2/Slc6a13 were measured. TAUT and GAT2 showed strong [14C]hypotaurine uptake activity, while BGT1 showed moderate activity, and GAT1 and GAT3 showed slight but significant activity. Mouse TAUT and GAT2 both showed Michaelis constants of 11 μM for hypotaurine uptake. GAT2-expressing cells pretreated with hypotaurine showed resistance to H2O2-induced oxidative stress. These results suggest that under physiological conditions, TAUT and GAT2 would be major contributors to hypotaurine transfer across the plasma membrane, and that uptake of hypotaurine via GAT2 contributes to the cellular resistance to oxidative stress.

Original languageEnglish
Pages (from-to)1523-1529
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume41
Issue number10
DOIs
Publication statusPublished - 2018 Jan 1

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Acids
Cysteamine
Taurine
Oxidative Stress
hypotaurine
Dioxygenases
HEK293 Cells
Antioxidants
Cell Membrane

Keywords

  • antioxidant
  • gamma-aminobutyric acid (GABA)
  • hypotaurine
  • taurine
  • transporter

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Nishimura, T., Higuchi, K., Yoshida, Y., Sugita-Fujisawa, Y., Kojima, K., Sugimoto, M., ... Nakashima, E. (2018). Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6. Biological and Pharmaceutical Bulletin, 41(10), 1523-1529. https://doi.org/10.1248/bpb.b18-00168

Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6. / Nishimura, Tomohiro; Higuchi, Kei; Yoshida, Yuko; Sugita-Fujisawa, Yuki; Kojima, Kazuaki; Sugimoto, Maiko; Santo, Marie; Tomi, Masatoshi; Nakashima, Emi.

In: Biological and Pharmaceutical Bulletin, Vol. 41, No. 10, 01.01.2018, p. 1523-1529.

Research output: Contribution to journalArticle

Nishimura, T, Higuchi, K, Yoshida, Y, Sugita-Fujisawa, Y, Kojima, K, Sugimoto, M, Santo, M, Tomi, M & Nakashima, E 2018, 'Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6', Biological and Pharmaceutical Bulletin, vol. 41, no. 10, pp. 1523-1529. https://doi.org/10.1248/bpb.b18-00168
Nishimura, Tomohiro ; Higuchi, Kei ; Yoshida, Yuko ; Sugita-Fujisawa, Yuki ; Kojima, Kazuaki ; Sugimoto, Maiko ; Santo, Marie ; Tomi, Masatoshi ; Nakashima, Emi. / Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6. In: Biological and Pharmaceutical Bulletin. 2018 ; Vol. 41, No. 10. pp. 1523-1529.
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