Roles of TauT and system A in cytoprotection of rat syncytiotrophoblast cell line exposed to hypertonic stress.
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.
Nishimura
T
T
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. nakashima-em@pha.keio.ac.jp
Sai
Y
Y
Fujii
J
J
Muta
M
M
Iizasa
H
H
Tomi
M
M
Deureh
M
M
Kose
N
N
Nakashima
E
E
D026924:Amino Acid Transport System A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001622:Betaine / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006982:Hypertonic Solutions; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D049990:Membrane Transport Modulators / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D013312:Stress, Physiological; D013654:Taurine / Q000031:analogs & derivatives / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000099247:Taurine Transporters
D026924:Amino Acid Transport System A; D001622:Betaine; D006982:Hypertonic Solutions; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013654:Taurine; D015091:beta-Alanine; D000099247:Taurine Transporters; C012924:2,2-dimethyl-beta-alanine