Regulation of astrocytic glutamate transporter expression by Akt: evidence for a selective transcriptional effect on the GLT-1/EAAT2 subtype.

摘要: In the nervous system, astrocytes express different ratios of two glial glutamate transporters, transporter subtype 1 (GLT-1) and glutamate/aspartate (GLAST), but little is known about signaling pathways that independently regulate their expression. Treatment with dibutyryl-cAMP, epidermal growth factor (EGF) or other factors both induces expression GLT-1 increases GLAST in astrocyte cultures. The induction correlated morphological biochemical changes are consistent maturation. Pharmacological studies suggest phosphatidylinositol 3-kinase (PI-3K) nuclear transcription factor-kappaB (NF-kappaB) may be involved several systems Akt, also as protein kinase B (PKB), functions downstream PI-3K. these present we used lentiviral vectors engineered to dominant-negative (DN), constitutively active (CA), null variants Akt study possible involvement regulation GLT-1. Expression DN-Akt attenuated EGF-dependent CA-Akt caused a dose- time-dependent increase protein, increased mRNA levels, dihydrokainate-sensitive (presumably mediated) transport activity, change morphology more stellate shape, had no effect on levels. Finally, reporter construct containing putative promoter fragment from human homolog GLT-1, called EAAT2. From studies, conclude through can without increasing astrocytes.