Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Placenta. 2010 Nov;31(11):1003-9. doi: 10.1016/j.placenta.2010.08.003.
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 [(3)H]taurine and [(14)C]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. [(3)H]Taurine uptake was strongly inhibited by TauT inhibitors such as hypotaurine and β-alanine. MeAIB, a system A specific substrate, inhibited hypertonic stress-induced [(14)C]betaine uptake. These results suggest that TauT and system A play cytoprotective roles in syncytiotrophoblasts exposed to hypertonic stress.
本研究旨在阐明在受到高渗条件刺激的条件性永生化合体滋养层细胞系 (TR-TBT 18d-1) 中诱导的细胞保护机制。高渗诱导 TR-TBT 18d-1 细胞凋亡，但在培养基中添加 1mM 牛磺酸可阻断这种凋亡。使用 siRNA 敲低 TauT 表明，TauT 是 TR-TBT 18d-1 细胞摄取牛磺酸的主要贡献者，至少在正常条件下是这样。与正常条件相比，在高渗条件下培养的 TR-TBT 18d-1 细胞对 [(3)H]牛磺酸和 [(14)C]甜菜碱的细胞摄取增加。TauT、BGT-1、ATA2 和 HSP70mRNA 被高渗上调，而 OCTN2、ENT1 和 CNT1mRNA 被下调。TauT 抑制剂如次牛磺酸和 β-丙氨酸强烈抑制 [(3)H]牛磺酸摄取。MeAIB，一种系统 A 特异性底物，抑制高渗应激诱导的 [(14)C]甜菜碱摄取。这些结果表明 TauT 和系统 A 在暴露于高渗应激的合体滋养层细胞中发挥细胞保护作用。
