ENHANCED EXPRESSION OF THE BLOOD-BRAIN-BARRIER GLUT1 GLUCOSE-TRANSPORTER GENE BY BRAIN-DERIVED FACTORS

The blood-brain barrier GLUT1 glucose transporter is localized in brai n to the capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo. However, its expression is markedly downregulated in c ultured bovine brain capillary endothelium (ECL cells), possibly due t o the absence of brain-derived or astrocyte trophic factors in the tis sue culture medium. To examine this hypothesis, we studied the effect of a bovine brain homogenate (BBH), and conditioned media and plasma m embranes obtained from the rat C6 glioma cell line, on the abundance o f the GLUT1 transcript in ECL cells. BBH induced a significant increas e in the abundance of both GLUT1 and actin mRNAs, and this effect was dose and time dependent. The increase in the GLUT1 mRNA levels correla ted with an increase in the transcriptional rate of this gene measured by nuclear run-on experiments. C6 conditioned media and C6 plasma mem branes had no effect on the abundance of either GLUT1 or actin mRNA. T o determine whether known growth factors cause BBH-like induction of G LUT1 and actin mRNAs, a series of growth factors was also tested. EGF and PDGF had no effect on the levels of these mRNAs. Basic FGF had a m oderate effect and TNF alpha partially mimicked the effect of BBH on b oth GLUT1 and actin transcripts. The present data suggests that brain- derived trophic factors present in BBH stimulate BBB-GLUT1 glucose tra nsporter gene expression in ECL cells through a transcriptional mechan ism. Although this effect was partially mimicked by TNF alpha, C6 cell membranes or C6 conditioned media were unable to induce changes in th e abundance of GLUT1 mRNA. Therefore, BBH may be a useful model to stu dy the characterization of soluble brain-derived trophic factors invol ved in the induction of BBB-GLUT1 gene expression.