Transport mechanism for aluminum citrate at the blood-brain barrier: kinetic evidence implies involvement of system Xc− in immortalized rat brain endothelial cells

Although accumulation of aluminum (Al) in the brain is known to cause neurodegenerative disorders and to be regulated mainly by the blood-brain barrier (BBB), the mechanism responsible for Al transport at the BBB has not been clarified yet. In this study, we investigated what kind of transporter is involved in the transport of Al citrate, which is the major species of Al in the brain, at the BBB using a rat immortalized brain endothelial cell line (RBEC1), focusing on the glutamate transporter family. The uptake of Al citrate showed temperature- and concentration-dependency, and did not require an inwardly directed Na+-gradient as a driving force, ruling out the involvement of Na+-dependent glutamate transporters in its transport. By RT-PCR, in RBEC1, there were mRNAs for the components of a Na+-independent glutamate transporter, system Xc−. l-Glutamate and l-cystine, representative ligands for system Xc−, significantly inhibited the uptake of Al citrate, and loading of them into the cells resulted in stimulation of its uptake in RBEC1. These results demonstrated that Al citrate is taken up into RBEC1 via system Xc−, and that this system might play an important role in Al citrate transport at the BBB.