Roles of TauT and system A in cytoprotection of rat syncytiotrophoblast cell line exposed to hypertonic stress

Abstract 

The purpose of this study was to clarify the cytoprotective mechanism(s) induced in a conditionally immortalized syncytiotrophoblast cell line (TR-TBT 18d-1) exposed to hypertonic conditions. Hypertonicity-induced apoptosis of TR-TBT 18d-1 cells, but this was blocked by addition of 1 mM taurine to the culture medium. TauT-knockdown using siRNA revealed that TauT is a major contributor to taurine uptake by TR-TBT 18d-1 cells, at least under normal conditions. Cellular uptake of [³H]taurine and [¹⁴C]betaine by TR-TBT 18d-1 cells cultured under hypertonic conditions was increased compared to that under normal conditions. TauT, BGT-1, ATA2 and HSP70 mRNAs were upregulated by hypertonicity, while OCTN2, ENT1 and CNT1 mRNAs were downregulated. [³H]Taurine uptake was strongly inhibited by TauT inhibitors such as hypotaurine and β-alanine. MeAIB, a system A specific substrate, inhibited hypertonic stress-induced [¹⁴C]betaine uptake. These results suggest that TauT and system A play cytoprotective roles in syncytiotrophoblasts exposed to hypertonic stress.

Keywords: Syncytiotrophoblast, Taurine, Betaine, Hypertonicity, System A, TauT

Abbreviations: ATA2, amino acid transporter 2, BGT-1, betaine/GABA transporter, CNT2, concentrative nucleoside transporter 2, ENT1, equilibrative nucleoside transporter 1, G3PDH, glyceraldehyde-3-phosphate dehydrogenase, HSP70, heat-shock protein 70, MeAIB, 2-methylaminoisobutyric acid, OCTN2, organic cation/carnitine transporter, TauT, taurine transporter, TonEBP, tonicity-responsive enhancer binding protein