Disease relevance of Slc1a2

• The glutamate transporter GLT-1 from Rattus norvegicus was expressed at high level in BHK cells using the Semliki Forest virus expression system [1].
• Further real-time quantitative RT-PCR assays showed that global ischemia resulted in a decrease in GLT-1 mRNA level of hippocampal CA1 region [2].
• These results suggested that astrocytic GLT-1 participated in the clearance of extracellular Glu and protected neurons from NMDA receptor-mediated toxicity [3].
• Bilateral infusion of the recombinant adenoviruses into the NAc shell efficiently increased GLT-1 expression surrounding the infusion site, at least during the period 2-8 days after the infusion [4].
• Consistent with these data, C6 glioma expressed EAAC1- but not GLT1- and GLAST-like immunoreactivity [5].

Psychiatry related information on Slc1a2

• These findings support the possibility that glutamate transporters such as GLT-1 are involved in morphine dependence [6].
• The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Abeta1-42 [7].
• Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernicke's encephalopathy [8].

High impact information on Slc1a2

• Here, we describe the determination of the membrane topology of the cloned astroglial glutamate transporter GLT-1 [9].
• Biotinylation of single cysteine mutants of the glutamate transporter GLT-1 from rat brain reveals its unusual topology [9].
• Three glutamate transporters have been identified in rat, including astroglial transporters GLAST and GLT-1 and a neuronal transporter EAAC1 [10].
• GLT-1 was much higher in hippocampal astrocytes than in cerebellar astrocytes [11].
• GLT-1 is distributed in astrocytes throughout the brain and spinal cord [12].

Chemical compound and disease context of Slc1a2

• In the present study, we examined the effects of gene transfer of a glial glutamate transporter, GLT-1, into the NAc shell by recombinant adenoviruses on methamphetamine- and morphine-induced conditioned place preference in rats [4].
• This study presents a northern blot analysis of the GLT-1 glutamate transporter in hyperammonemic rats, and in rats with thioacetamide-induced acute liver failure [13].
• The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the extracellular levels of amino acids and energy metabolites in a model of iron-induced posttraumatic epilepsy [14].
• In this study we used immuno-blotting technique to measure the cortical levels of the astrocytic glutamate transport protein (GLT-1) and of the glutamate and aspartate transporting protein (GLAST) in an epilepsy model induced by ferrous chloride injection in the cortex of rats [15].
• Vehicle, dihydrokainate (DHK, 1 mmol/L), a GLT-1 inhibitor, or tamoxifen (50 micromol/L), a VRAC inhibitor, were administered continuously via the dialysis probes starting one hour prior to ischemia [16].

Biological context of Slc1a2

• Up-regulation of GLT-1 expression was accompanied by an enhanced glutamate uptake, which could be blocked by the specific GLT-1 inhibitor dihydrokainate [17].
• Taken together, our data highlight a potential role for glucocorticoids in regulating GLT-1 gene expression during central nervous system development or pathophysiological processes including stress [17].
• GLT-1 is the predominant glutamate transporter in most brain regions and therefore plays a major role in terminating synaptic transmission and protecting neurons from glutamate neurotoxicity [18].
• Here, we describe the cDNA cloning of a variant of GLT1 from rat brain which is generated by alternative splicing at the 3'-end of the GLT1 cDNA [19].
• Here we show that PC-induced down-regulation of GLT-1 is crucial for the increased neuronal resistance to subsequent severe ischemic insult [20].

Anatomical context of Slc1a2

• Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptine [21].
• The synthetic glucocorticoid dexamethasone provoked a marked increase of GLT-1 transcription and protein levels in cortical astrocytes, whereas GLAST expression remained unaffected [17].
• Moreover, we monitored brain region-specific differences, since all corticosteroids used in this study failed to alter the expression of GLT-1 in midbrain and cerebellar glia, although expression levels of both corticosteroid receptor subtypes were similar in all brain regions analyzed [17].
• Glycosylated and non-glycosylated GLT-1 were transported to the plasma membrane with equal efficiency [1].
• For GLT-1 expressed in COS cells, coexpression of Ajuba did not affect the transporter's K(m) or V(max) for glutamate [22].

Associations of Slc1a2 with chemical compounds

• Accordingly, the current study examined the distribution and regulation of the glia glutamate transporter GLT-1 and the recently identified GLT isoform, GLT-1b, in the hippocampus of rats subjected to chronic restraint stress (CRS) [21].
• Dexamethasone, however, modestly enhanced GLT-1 expression in cerebellar glia in combination with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine, suggesting that suppression of GLT-1 expression in cerebellar cultures may at least in part be epigenetically mediated by a DNA methylation-dependent process [17].
• Histidine 326 is critical for the function of GLT-1, a (Na+ + K+)-coupled glutamate transporter from rat brain [23].
• The promoting effect of dexamethasone on GLT-1 gene expression and function was abolished by the GR antagonist mifepristone [17].
• A predominant role of the GR was further supported by the observation that corticosterone could elevate GLT-1 expression in a dose-dependent manner, whereas aldosterone, the physiological ligand of the mineralocorticoid receptor, exerted only weak effects even when applied at high concentrations [17].

Regulatory relationships of Slc1a2

• RNase protection assays showed that of the two glial transporters, mRNA for GLAST was expressed at much higher level than was GLT-1 [24].
• We suggest that one or both of the GLT-1 RNA species induced by Wnt-1 either fail to be translated or yield abnormal translation products that are quickly degraded [25].

Other interactions of Slc1a2

• In conclusion, this study highlights the occurrence of the reciprocal regulation of caveolin and GLT-1 expression during processes such as astrocyte differentiation via common signaling pathways [26].
• In apparent contrast, all factors completely failed to affect GLT-1 and GLAST expression in astroglial cultures from the cerebellum, mesencephalon, and spinal cord between 36 h and 7 days [27].
• Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha [28].
• These findings indicate that the induction of GLT-1 mRNA by HS is independent of the MAPK pathways [29].
• However, the possible functional role of EAAC1 in preventing neuron death has not been resolved as compared with glial glutamate transporters such as GLT-1 [30].

Analytical, diagnostic and therapeutic context of Slc1a2

• The low-resolution structure of GLT-1 was determined by electron microscopy and single particle reconstruction [1].
• Western blotting analysis indicated that transient global ischemia decreased the protein level of GLT-1 in the hippocampal CA1 area without affecting GLAST protein level [2].
• Selective blockade of astrocytic glutamate transporter GLT-1 with dihydrokainate prevents neuronal death during ouabain treatment of astrocyte/neuron cocultures [3].
• In situ hybridization using cRNA and oligonucleotide probes, and immunocytochemistry using an antibody against a synthetic GLT1v peptide were applied in order to identify the cell types expressing GLT1 variant in the adult rat nervous system [19].
• Northern blot analysis showed that in brain the mRNA of GLT1 (approximately 11 kb) is predominant while in the retina the mRNA of GLT1 variant (approximately 12.5 kb) prevails [19].

References