title: Retinoic acid mediates the expression of glutamate transporter-1 in rat astrocytes through genomic RXR action and non-genomic protein kinase C signaling pathway.
abstract: Astrocytic glutamate transporter-1 (GLT-1) is responsible for 90% of forebrain glutamate uptake in the adult CNS. Retinoic acid (RA) is a potent regulator of neural cell differentiation and neuronal maturation in the developing CNS through activation of RA receptors/retinoic X receptors (RXRs) or non-genomic mechanisms. Although rat GLT-1 contains several RXR binding regions, RA-triggered RXR mechanisms regulating GLT-1 expression remain unknown. RA applied at submicromolar concentrations for 24 h significantly reduced GLT-1 mRNA and membrane levels in astrocytes and dibutyryl cAMP (dbcAMP)-primed astrocytes. An RXR agonist reduced astrocytic GLT-1 mRNA expression, whereas an RXR antagonist blocked the effects of RA on the reduction of astrocytic GLT-1 mRNA expression. Electrophoresis motility shift assay indicated that RA-treatment increased astrocytic RXR-DNA binding activity. RA-induced reduction in GLT-1 mRNA expression was also observed in dbcAMP-primed astrocytes. Through lentivirus-mediated astrocytic over-expression of rat GLT-1, levels of GLT-1 in the processes of dbcAMP-treated astrocytes were attenuated by exposure to RA. The protein kinase C inhibitor, Bis I, restored GLT-1 distribution in the processes of RA-treated dbcAMP-primed astrocytes. These results suggest that RA reduces astrocytic GLT-1 levels through both RXR-mediated inhibition at the transcriptional level and triggering activation of protein kinase C which reduces cell surface GLT-1 levels.
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ti-Ju
authors.initials: TJ
authors.lastname: Chan
authors.forename: Lu-Shiun
authors.initials: LS
authors.lastname: Her
authors.forename: Hung-Jiun
authors.initials: HJ
authors.lastname: Liaw
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Chen
authors.forename: Shun-Fen
authors.initials: SF
authors.lastname: Tzeng
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D006579:Heterozygote; D016086:Lentivirus / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism; D047488:Retinoid X Receptors / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000199:Actins; D018076:DNA, Complementary; D027341:Excitatory Amino Acid Transporter 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D047488:Retinoid X Receptors; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid; D014212:Tretinoin; D003994:Bucladesine; D011493:Protein Kinase C