BRAIN-DERIVED PEPTIDES INCREASE BLOOD-BRAIN-BARRIER GLUT1 GLUCOSE-TRANSPORTER GENE-EXPRESSION VIA MESSENGER-RNA STABILIZATION

The present investigation studied the effect of the brain-derived pept ide preparation Cerebrolysin (CI, EBEWE, Austria) on the turnover rate and gene expression of the blood-brain barrier (BBB) GLUT1 glucose tr ansporter mRNA. Studies were performed in brain endothelial cultured c ells transfected with the human (h) GLUT1 transcript. In control cells , the full length 2.8 Kb hGLUT1 mRNA was rapidly degraded following tr ansfection, and the abundance of this transcript at 4 and 6 h was comp arable to background mRNA levels seen in cells transfected without hGL UT1 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 par allel experiments, CI induced a significant increase in the levels of immunoreactive GLUT1 protein measured by enzyme-linked immunosorbent a ssay (ELISA). In conclusion, data presented here demonstrate that fact ors in CI increase BBB-GLUT1 transcript stability, and that this is as sociated with an induction of BBB-GLUT1 gene expression in brain endot helial cultured cells. (C) 1998 Elsevier Science Ireland Ltd. All righ ts reserved.