Regulation of taurine transport at the blood-brain barrier by tumor necrosis factor-alpha, taurine and hypertonicity.
Taurine is the abundant sulfur-containing beta-amino acid in brain where it exerts a neuroprotective effect. Although it is known that the blood-brain barrier (BBB) mediates taurine transport, the regulation of taurine transport have not been clarified yet. A conditionally immortalized rat brain capillary endothelial cells (TR-BBB13), an in vitro model of the BBB, exhibited [3H]taurine uptake, which was dependent on both Na+ and Cl-, and inhibited by beta-alanine. Taurine transporter (TAUT) mRNA was detected in TR-BBB13 cells, and TAUT protein was also expressed at 70 kDa. TR-BBB13 cells exposed to 20 ng/mL TNF-alpha and under hypertonic conditions showed a 1.7-fold and 3.2-fold increase in [3H]taurine uptake, respectively. In contrast, lipopolysaccharide and diethyl maleate did not significantly affect taurine uptake. The taurine uptake was reduced by pre-treatment with excess taurine (50 mm). The mRNA level of the TAUT in TNF-alpha and following hypertonic treatment was greater than that in control cells, whereas that under excess taurine conditions was lower than in controls. Therefore, taurine transport activity at the BBB appears to be regulated at the transcriptional level by cell damage, osmolality and taurine in the brain.
Kang
Young-Sook
YS
College of Pharmacy, Sookmyung Women's University, Seoul, Korea New Industry Creation Hatchery Center, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan.
Ohtsuki
Sumio
S
Takanaga
Hitomi
H
Tomi
Masatoshi
M
Hosoya
Ken-Ichi
K
Terasaki
Tetsuya
T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006982:Hypertonic Solutions / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013654:Taurine / Q000378:metabolism* / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014882:Water-Electrolyte Balance; D015091:beta-Alanine / Q000494:pharmacology; D000099247:Taurine Transporters
D002352:Carrier Proteins; D002712:Chlorides; D006982:Hypertonic Solutions; D008070:Lipopolysaccharides; D008298:Maleates; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D012964:Sodium; D013654:Taurine; D014409:Tumor Necrosis Factor-alpha; D015091:beta-Alanine; D000099247:Taurine Transporters; C014476:diethyl maleate