Post-transcription modulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived factors.
Brain-derived peptides or factors in the brain-derived preparation Cerebrolysin (Cl, EBEWE, Austria) increase the expression of the blood-brain barrier (BBB) GLUT1 glucose transporter via mRNA stabilization. The post-transcriptional regulation of the BBB-GLUT1 gene is principally exerted by interaction of cis-regulatory elements located in the 3'-untranslated region of GLUT1 mRNA with cellular trans-acting factors (TAF). UV-cross linking and RNase T1 protection studies demonstrated the presence of 2 major GLUT1 RNA-TAF complexes named p88 (stabilizing) and the p44 (destabilizing). The p88 TAF was detected in cytosol of brain endothelial cultured cells (ECL) as a duplex of molecular weight of approximately 88 kDa, which were defined A and B (high and low MW, respectively). Cl markedly increased the abundance of the BBB-GLUT1 p88 TAF (complex B) in ECL cells, without changes in the levels of the p88 complex A. This was also confirmed by antisense oligomer displacement of the GLUT1 RNA-TAF complex formation. Cl per se, did not bind to the GLUT1 mRNA, nor induced the expression of the destabilizing p44 TAF. Data presented here suggest that the increased stabilization of the GLUT1 transcript induced by Cl is associated with augmented levels of the GLUT1 stabilizing p88 TAF.
Boado
R J
RJ
Department of Medicine and Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.
D020413:3' Untranslated Regions / Q000502:physiology; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier; D002417:Cattle; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1; D008970:Molecular Weight; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D018697:Nootropic Agents / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology
D020413:3' Untranslated Regions; D000596:Amino Acids; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D018697:Nootropic Agents; D012333:RNA, Messenger; D015534:Trans-Activators; C006952:cerebrolysin