Molecular regulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides.

Abstract

The blood-brain barrier (BBB) GLUT1 glucose transporter represents the limiting step in transport of glucose from blood to brain, and its activity has been shown to be altered in different pathophysiological conditions such as hypoglycemia, brain tumors, development, and Alzheimer’s disease. The molecular regulation of the BBB-GLUT1 gene is directed at both transcription and post-transcriptional stabilization of mRNA by brain-derived factors present in a bovine brain homogenate [Boado, et al. (1994) Mol Brain Res 22: 259] and in the brain-derived peptide rich preparation Cerebrolysin® (CL, EBEWE, Austria) [Boado (1994) Eur J Neurosci [Suppl] 7: 58], respectively. Since increased GLUT1 mRNA stability was correlated with augmented GLUT1 immunoreactive protein in hypoglycemia and with the antidiabetic agent pioglitazone, it is possible that Cl increases the translation efficiency of BBB-GLUT1 transcript. Therefore, in order to test this hypothesis, the present investigation studied the effect of CL on the expression of the BBB-GLUT1 gene in brain endothelial cultured cells transfected with a luciferase expression vector containing the complete 171 nucleotides of the 5′-untranslated region of the human GLUT1 mRNA, which possesses the GLUT1 translational control elements. Dose response studies showed that Cl at concentrations of 1–10µl/m1 culture media produced a marked increase in the levels of luciferase (122–324% of control), whereas no significant changes were observed with 25 or 50 µl/ml.