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

• Published in: Placenta (Eastbourne) 2010-11, Vol.31 (11), p.1003-1009
• Main Authors: Nishimura, T, Sai, Y, Fujii, J, Muta, M, Iizasa, H, Tomi, M, Deureh, M, Kose, N, Nakashima, E
• Format: Article
• Language: English
• Subjects: Amino Acid Transport System A - antagonists & inhibitors; Amino Acid Transport System A - genetics; Amino Acid Transport System A - physiology; Animals; Apoptosis; beta-Alanine - analogs & derivatives; beta-Alanine - metabolism; beta-Alanine - pharmacology; Betaine; Betaine - metabolism; Biological and medical sciences; Biological Transport - drug effects; Cell Line; Cytoprotection; Embryology: invertebrates and vertebrates. Teratology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Gene Silencing; Hypertonic Solutions; Hypertonicity; Internal Medicine; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Membrane Transport Modulators - pharmacology; Membrane Transport Proteins - genetics; Membrane Transport Proteins - physiology; Obstetrics and Gynecology; Rats; RNA, Messenger - metabolism; RNA, Small Interfering; Stress, Physiological; Syncytiotrophoblast; System A; Taurine; Taurine - analogs & derivatives; Taurine - metabolism; TauT; Trophoblasts - drug effects; Trophoblasts - metabolism; Trophoblasts - pathology
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2010.08.003

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 [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.