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Retinoic acid mediates the expression of glutamate transporter‐1 in rat astrocytes through genomic RXR action and non‐genomic protein kinase C signaling pathway
Author(s) -
Chan TiJu,
Her LuShiun,
Liaw HungJiun,
Chen MeiChun,
Tzeng ShunFen
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07715.x
Subject(s) - retinoic acid , protein kinase c , signal transduction , microbiology and biotechnology , transporter , biology , chemistry , biochemistry , gene
J. Neurochem. (2012) 121 , 537–550. 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.