Brain-derived peptides increase blood-brain barrier GLUT1 glucose transporter gene expression via mRNA stabilization.
The present investigation studied the effect of the brain-derived peptide preparation Cerebrolysin (CI, EBEWE, Austria) on the turnover rate and gene expression of the blood-brain barrier (BBB) GLUT1 glucose transporter mRNA. Studies were performed in brain endothelial cultured cells transfected with the human (h) GLUT1 transcript. In control cells, the full length 2.8 Kb hGLUT1 mRNA was rapidly degraded following transfection, and the abundance of this transcript at 4 and 6 h was comparable to background mRNA levels seen in cells transfected without hGLUT1 mRNA. On the contrary, the decay of the hGLUT1 mRNA was stabilized in CI-treated cells resulting in a marked reduction in the fractional turnover rate (72.4 and 4.0%/h, control and CI, respectively). In parallel experiments, CI induced a significant increase in the levels of immunoreactive GLUT1 protein measured by enzyme-linked immunosorbent assay (ELISA). In conclusion, data presented here demonstrate that factors in CI increase BBB-GLUT1 transcript stability, and that this is associated with an induction of BBB-GLUT1 gene expression in brain endothelial cultured cells.
Boado
R J
RJ
Department of Medicine and Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA. rboado@med1.medsch.ucla.edu
D000596:Amino Acids / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000502:physiology; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D051272:Glucose Transporter Type 1; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
D000596:Amino Acids; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C006952:cerebrolysin