Distribution of Cystine/Glutamate Exchange Transporter, System x_c⁻, in the Mouse Brain

Abstract

Mammalian cells express a transport system known as system x(c)-, which is an exchange agency specific for anionic forms of cystine and glutamate. System x(c)- activity is important to maintain both intracellular glutathione levels and the redox balance between cystine and cysteine in the extracellular milieu. We have shown that the cloned cDNAs encoding the transporter for system x(c)- consist of two components, xCT and the heavy chain of 4F2 antigen. In the present study, we have investigated the mRNA distribution for these components in the mouse brain by in situ hybridization. The xCT mRNA was expressed in the area postrema, subfornical organ, habenular nucleus, hypothalamic area, and ependymal cells of the lateral wall of the third ventricle in the adult mouse brain. A strong signal was also detected in the meninges in both adult and fetal mouse brains. The mRNA expression of the heavy chain of 4F2 antigen was detected in a more broad area, including all of the regions in which xCT mRNA was detected. These data are compatible with our biochemical evidence that xCT functions in combination with the heavy chain of 4F2 antigen to elicit system x(c)- activity. The expression of system x(c)- in meninges and some circumventricular organs may suggest that this transporter contributes to the maintenance of the redox state (i.e., cysteine/cystine ratio) in the CSF.