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

  • R. J. Boado
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


Glucose is the crucial metabolic fluid for the brain, and the transport of this nutrient from blood to brain is limited by the blood-brain barrier (BBB) GLUT1 glucose transporter. The activity of this transporter is altered in different pathophysiological conditions including Alzheimer’s disease. The expression of the BBB-GLUT1 gene is directed by brain trophic factors, and the brain-derived peptide preparation Cerebrolysin® (Cl, EBEWE, Austria), used in the treatment of Alzheimer’s disease, increases the BBB-GLUT1 mRNA stability and the expression of the BBB-GLUT1 gene. In the present investigation, Cl markedly increased (p < 0.001) the expression of a BBB-GLUT1 reporter gene, named clone 753, that contains an important regulatory cis-acting element involved in the stabilization of this transcript in brain endothelial cultured cells (ECL). In experiments with a reporter gene lacking this regulatory element, Cl produced only a minimal fraction of the effect observed with clone 753. UV-cross linking/PAGE experiments showed that the GLUT1 transcript reacts with ECL cytosolic proteins to form a RNA/protein complex of ~80kDa. The abundance of this cis/trans acting complex was found to be increased in Cl-treated cells. Overall, data presented here demonstrate that i) Cl increases the expression of a BBB-GLUT1-luciferase reporter gene containing a region of the 3′-untranslated region of BBB-GLUT1 mRNA with important regulatory cis-acting elements involved in the stabilization of this transcript, and ii) the increased expression of this BBB-GLUT1 reporter gene was associated with augmented abundance of a transacting factor that binds to the cis-acting element described in (i), suggesting that this association may be involved in the stabilization of GLUT1 mRNA induced by Cl.


Reporter Gene GLUT1 Glucose Transporter GLUT1 mRNA Sequence Specific Manner GLUT1 Gene 
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Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • R. J. Boado
    • 1
    • 2
  1. 1.Department of Medicine and Brain Research InstituteUCLA School of MedicineLos AngelesUSA
  2. 2.Department of MedicineUCLA School of MedicineLos AngelesUSA

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