4.3 Article Proceedings Paper

Hypotaurine Is a Substrate of GABA Transporter Family Members GAT2/Slc6a13 and TAUT/Slc6a6

Journal

BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 41, Issue 10, Pages 1523-1529

Publisher

PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b18-00168

Keywords

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

Funding

  1. JSPS KAKENHI [15K15007, 15K08595, 26282028]
  2. Ministry of Education, Culture, Sports, Science and Technology (MEXT)
  3. Uehara Memorial Foundation
  4. Keio Gijuku Academic Development Funds
  5. Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research
  6. Grants-in-Aid for Scientific Research [15K15007, 15K08595, 26282028] Funding Source: KAKEN

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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/gamma-aminobutyric acid (GABA) transporter family members. Radiolabeled hypotaurine was synthesized from radiolabeled cysteamine and 2-aminoethanethiol dioxygenase. The uptakes of [H-3]GABA, [H-3]taurine, and [C-14]hypotaurine by HEK293 cells expressing mouse GAT1/Slc6a1, TAUT/Slc6a6, GAT3/Slc6a11, BGT1/Slc6a12, and GAT2/Slc6a13 were measured. TAUT and GAT2 showed strong [C-14]hypotaurine uptake activity, while BGT1 showed moderate activity, and GATT and GAT3 showed slight but significant activity. Mouse TAUT and GAT2 both showed Michaelis constants of 11 mu m 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.

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