Log in

Relevant bibliographies by topics / EAAT4 / Journal articles

To see the other types of publications on this topic, follow the link: EAAT4.

Journal articles on the topic 'EAAT4'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'EAAT4.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Abousaab, Abeer, and Florian Lang. "Up-Regulation of Excitatory Amino Acid Transporters EAAT3 and EAAT4 by Lithium Sensitive Glycogen Synthase Kinase GSK3ß." Cellular Physiology and Biochemistry 40, no. 5 (2016): 1252–60. http://dx.doi.org/10.1159/000453179.

Full text

Abstract:

Background: Cellular uptake of glutamate by the excitatory amino-acid transporters (EAATs) decreases excitation and thus participates in the regulation of neuroexcitability. Kinases impacting on neuronal function include Lithium-sensitive glycogen synthase kinase GSK3ß. The present study thus explored whether the activities of EAAT3 and/or EAAT4 isoforms are sensitive to GSK3ß. Methods: cRNA encoding wild type EAAT3 (SLC1A1) or EAAT4 (SLC1A6) was injected into Xenopus oocytes without or with additional injection of cRNA encoding wild type GSK3ß or the inactive mutant K85AGSK3ß. Dual electrode voltage clamp was performed in order to determine glutamate-induced current (IEAAT). Results: Appreciable IEAAT was observed in EAAT3 or EAAT4 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of GSK3ß but not by coexpression of K85AGSK3ß. Coexpression of GSK3ß increased significantly the maximal IEAAT in EAAT3 or EAAT4 expressing oocytes, without significantly modifying apparent affinity of the carriers. Lithium (1 mM) exposure for 24 hours decreased IEAAT in EAAT3 and GSK3ß expressing oocytes to values similar to IEAAT in oocytes expressing EAAT3 alone. Lithium did not significantly modify IEAAT in oocytes expressing EAAT3 without GSK3ß. Conclusions: Lithium-sensitive GSK3ß is a powerful regulator of excitatory amino acid transporters EAAT3 and EAAT4.

APA, Harvard, Vancouver, ISO, and other styles

2

Abousaab, Abeer, Jamshed Warsi, Bernat Elvira, and Florian Lang. "Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters EAAT1, EAAT2, EAAT3, and EAAT4." Journal of Membrane Biology 249, no. 3 (2015): 239–49. http://dx.doi.org/10.1007/s00232-015-9863-0.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Fang, Hongyu, Yueming Huang, and Zhiyi Zuo. "Enhancement of substrate-gated Cl− currents via rat glutamate transporter EAAT4 by PMA." American Journal of Physiology-Cell Physiology 290, no. 5 (2006): C1334—C1340. http://dx.doi.org/10.1152/ajpcell.00443.2005.

Full text

Abstract:

Glutamate transporters (also called excitatory amino acid transporters, EAAT) are important in extracellular homeostasis of glutamate, a major excitatory neurotransmitter. EAAT4, a neuronally expressed EAAT in cerebellum, has a large portion (∼95% of the total l-aspartate-induced currents in human EAAT4) of substrate-gated Cl− currents, a distinct feature of this EAAT. We cloned EAAT4 from rat cerebellum. This molecule was predicted to have eight putative transmembrane domains. l-Glutamate induced an inward current in oocytes expressing this EAAT4 at a holding potential −60 mV. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, significantly increased the magnitude of l-glutamate-induced currents but did not affect the apparent affinity of EAAT4 for l-glutamate. This PMA-enhanced current had a reversal potential −17 mV at extracellular Cl− concentration ([Cl−]o) 104 mM with an ∼60-mV shift per 10-fold change in [Cl−]o, properties consistent with Cl−-selective conductance. However, PMA did not change EAAT4 transport activity as measured by [3H]-l-glutamate. Thus PMA-enhanced Cl− currents via EAAT4 were not thermodynamically coupled to substrate transport. These PMA-enhanced Cl− currents were partially blocked by staurosporine, chelerythrine, and calphostin C, the three PKC inhibitors. Ro-31-8425, a PKC inhibitor that inhibits conventional PKC isozymes at low concentrations (nM level), partially inhibited the PMA-enhanced Cl− currents only at a high concentration (1 μM). Intracellular injection of BAPTA, a Ca2+-chelating agent, did not affect the PMA-enhanced Cl− currents. 4α-Phorbol-12,13-didecanoate, an inactive analog of PMA, did not enhance glutamate-induced currents. These data suggest that PKC, possibly isozymes other than conventional ones, modulates the substrate-gated Cl− currents via rat EAAT4. Our results also suggest that substrate-gated ion channel activity and glutamate transport activity, two EAAT4 properties that could modulate neuronal excitability, can be regulated independently.

APA, Harvard, Vancouver, ISO, and other styles

4

Søgaard, Rikke, Ivana Novak, and Nanna MacAulay. "Elevated ammonium levels: differential acute effects on three glutamate transporter isoforms." American Journal of Physiology-Cell Physiology 302, no. 6 (2012): C880—C891. http://dx.doi.org/10.1152/ajpcell.00238.2011.

Full text

Abstract:

Increased ammonium (NH4+/NH3) in the brain is a significant factor in the pathophysiology of hepatic encephalopathy, which involves altered glutamatergic neurotransmission. In glial cell cultures and brain slices, glutamate uptake either decreases or increases following acute ammonium exposure but the factors responsible for the opposing effects are unknown. Excitatory amino acid transporter isoforms EAAT1, EAAT2, and EAAT3 were expressed in Xenopus oocytes to study effects of ammonium exposure on their individual function. Ammonium increased EAAT1- and EAAT3-mediated [3H]glutamate uptake and glutamate transport currents but had no effect on EAAT2. The maximal EAAT3-mediated glutamate transport current was increased but the apparent affinities for glutamate and Na+ were unaltered. Ammonium did not affect EAAT3-mediated transient currents, indicating that EAAT3 surface expression was not enhanced. The ammonium-induced stimulation of EAAT3 increased with increasing extracellular pH, suggesting that the gaseous form NH3 mediates the effect. An ammonium-induced intracellular alkalinization was excluded as the cause of the enhanced EAAT3 activity because 1) ammonium acidified the oocyte cytoplasm, 2) intracellular pH buffering with MOPS did not reduce the stimulation, and 3) ammonium enhanced pH-independent cysteine transport. Our data suggest that the ammonium-elicited uptake stimulation is not caused by intracellular alkalinization or changes in the concentrations of cotransported ions but may be due to a direct effect on EAAT1/EAAT3. We predict that EAAT isoform-specific effects of ammonium combined with cell-specific differences in EAAT isoform expression may explain the conflicting reports on ammonium-induced changes in glial glutamate uptake.

APA, Harvard, Vancouver, ISO, and other styles

5

Schneider, Nicole, Sönke Cordeiro, Jan-Philipp Machtens, Simona Braams, Thomas Rauen, and Christoph Fahlke. "Functional Properties of the Retinal Glutamate Transporters GLT-1c and EAAT5." Journal of Biological Chemistry 289, no. 3 (2013): 1815–24. http://dx.doi.org/10.1074/jbc.m113.517177.

Full text

Abstract:

In the mammalian retina, glutamate uptake is mediated by members of a family of glutamate transporters known as “excitatory amino acid transporters (EAATs).” Here we cloned and functionally characterized two retinal EAATs from mouse, the GLT-1/EAAT2 splice variant GLT-1c, and EAAT5. EAATs are glutamate transporters and anion-selective ion channels, and we used heterologous expression in mammalian cells, patch-clamp recordings and noise analysis to study and compare glutamate transport and anion channel properties of both EAAT isoforms. We found GLT-1c to be an effective glutamate transporter with high affinity for Na+ and glutamate that resembles original GLT-1/EAAT2 in all tested functional aspects. EAAT5 exhibits glutamate transport rates too low to be accurately measured in our experimental system, with significantly lower affinities for Na+ and glutamate than GLT-1c. Non-stationary noise analysis demonstrated that GLT-1c and EAAT5 also differ in single-channel current amplitudes of associated anion channels. Unitary current amplitudes of EAAT5 anion channels turned out to be approximately twice as high as single-channel amplitudes of GLT-1c. Moreover, at negative potentials open probabilities of EAAT5 anion channels were much larger than for GLT-1c. Our data illustrate unique functional properties of EAAT5, being a low-affinity and low-capacity glutamate transport system, with an anion channel optimized for anion conduction in the negative voltage range.

APA, Harvard, Vancouver, ISO, and other styles

6

Mim, Carsten, Poonam Balani, Thomas Rauen, and Christof Grewer. "The Glutamate Transporter Subtypes EAAT4 and EAATs 1-3 Transport Glutamate with Dramatically Different Kinetics and Voltage Dependence but Share a Common Uptake Mechanism." Journal of General Physiology 126, no. 6 (2005): 571–89. http://dx.doi.org/10.1085/jgp.200509365.

Full text

Abstract:

Here, we report the application of glutamate concentration jumps and voltage jumps to determine the kinetics of rapid reaction steps of excitatory amino acid transporter subtype 4 (EAAT4) with a 100-μs time resolution. EAAT4 was expressed in HEK293 cells, and the electrogenic transport and anion currents were measured using the patch-clamp method. At steady state, EAAT4 was activated by glutamate and Na+ with high affinities of 0.6 μM and 8.4 mM, respectively, and showed kinetics consistent with sequential binding of Na+-glutamate-Na+. The steady-state cycle time of EAAT4 was estimated to be &gt;300 ms (at −90 mV). Applying step changes to the transmembrane potential, Vm, of EAAT4-expressing cells resulted in the generation of transient anion currents (decaying with a τ of ∼15 ms), indicating inhibition of steady-state EAAT4 activity at negative voltages (&lt;−40 mV) and activation at positive Vm (&gt;0 mV). A similar inhibitory effect at Vm &lt; 0 mV was seen when the electrogenic glutamate transport current was monitored, resulting in a bell-shaped I-Vm curve. Jumping the glutamate concentration to 100 μM generated biphasic, saturable transient transport and anion currents (Km ∼ 5 μM) that decayed within 100 ms, indicating the existence of two separate electrogenic reaction steps. The fast electrogenic reaction was assigned to Na+ binding to EAAT4, whereas the second reaction is most likely associated with glutamate translocation. Together, these results suggest that glutamate uptake of EAAT4 is based on the same molecular mechanism as transport by the subtypes EAATs 1–3, but that its kinetics and voltage dependence are dramatically different from the other subtypes. EAAT4 kinetics appear to be optimized for high affinity binding of glutamate, but not rapid turnover. Therefore, we propose that EAAT4 is a high-affinity/low-capacity transport system, supplementing low-affinity/high-capacity synaptic glutamate uptake by the other subtypes.

APA, Harvard, Vancouver, ISO, and other styles

7

Abousaab, Abeer, Nestor Luis Uzcategui, Bhaeldin Elsir, and Florian Lang. "Up-Regulation of the Excitatory Amino Acid Transporters EAAT1 and EAAT2 by Mammalian Target of Rapamycin." Cellular Physiology and Biochemistry 39, no. 6 (2016): 2492–500. http://dx.doi.org/10.1159/000452516.

Full text

Abstract:

Background: The excitatory amino-acid transporters EAAT1 and EAAT2 clear glutamate from the synaptic cleft and thus terminate neuronal excitation. The carriers are subject to regulation by various kinases. The EAAT3 isoform is regulated by mammalian target of rapamycin (mTOR). The present study thus explored whether mTOR influences transport by EAAT1 and/or EAAT2. Methods: cRNA encoding wild type EAAT1 (SLC1A3) or EAAT2 (SLC1A2) was injected into Xenopus oocytes without or with additional injection of cRNA encoding mTOR. Dual electrode voltage clamp was performed in order to determine electrogenic glutamate transport (IEAAT). EAAT2 protein abundance was determined utilizing chemiluminescence. Results: Appreciable IEAAT was observed in EAAT1 or EAAT2 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of mTOR. Coexpression of mTOR increased significantly the maximal IEAAT in EAAT1 or EAAT2 expressing oocytes, without significantly modifying affinity of the carriers. Moreover, coexpression of mTOR increased significantly EAAT2 protein abundance in the cell membrane. Conclusions: The kinase mTOR up-regulates the excitatory amino acid transporters EAAT1 and EAAT2.

APA, Harvard, Vancouver, ISO, and other styles

8

Hu, Qiu Xiang, Sigrid Ottestad-Hansen, Silvia Holmseth, Bjørnar Hassel, Niels Christian Danbolt, and Yun Zhou. "Expression of Glutamate Transporters in Mouse Liver, Kidney, and Intestine." Journal of Histochemistry & Cytochemistry 66, no. 3 (2018): 189–202. http://dx.doi.org/10.1369/0022155417749828.

Full text

Abstract:

Glutamate transport activities have been identified not only in the brain, but also in the liver, kidney, and intestine. Although glutamate transporter distributions in the central nervous system are fairly well known, there are still uncertainties with respect to the distribution of these transporters in peripheral organs. Quantitative information is mostly lacking, and few of the studies have included genetically modified animals as specificity controls. The present study provides validated qualitative and semi-quantitative data on the excitatory amino acid transporter (EAAT)1–3 subtypes in the mouse liver, kidney, and intestine. In agreement with the current view, we found high EAAT3 protein levels in the brush borders of both the distal small intestine and the renal proximal tubules. Neither EAAT1 nor EAAT2 was detected at significant levels in murine kidney or intestine. In contrast, the liver only expressed EAAT2 (but 2 C-terminal splice variants). EAAT2 was detected in the plasma membranes of perivenous hepatocytes. These cells also expressed glutamine synthetase. Conditional deletion of hepatic EAAT2 did neither lead to overt neurological disturbances nor development of fatty liver.

APA, Harvard, Vancouver, ISO, and other styles

9

Williams, Brent L., Kavitha Yaddanapudi, Mady Hornig, and W. Ian Lipkin. "Spatiotemporal Analysis of Purkinje Cell Degeneration Relative to Parasagittal Expression Domains in a Model of Neonatal Viral Infection." Journal of Virology 81, no. 6 (2006): 2675–87. http://dx.doi.org/10.1128/jvi.02245-06.

Full text

Abstract:

ABSTRACT Infection of newborn Lewis rats with Borna disease virus (neonatal Borna disease [NBD]) results in cerebellar damage without the cellular inflammation associated with infections in later life. Purkinje cell (PC) damage has been reported for several models of early-life viral infection, including NBD; however, the time course and distribution of PC pathology have not been investigated rigorously. This study examined the spatiotemporal relationship between PC death and zonal organization in NBD cerebella. Real-time PCR at postnatal day 28 (PND28) revealed decreased cerebellar levels of mRNAs encoding the glycolytic enzymes aldolase C (AldoC, also known as zebrin II) and phosphofructokinase C and the excitatory amino acid transporter 4 (EAAT4). Zebrin II and EAAT4 immunofluorescence analysis in PND21, PND28, PND42, and PND84 NBD rat cerebella revealed a complex pattern of PC degeneration. Early cell loss (PND28) was characterized by preferential apoptotic loss of zebrin II/EAAT4-negative PC subsets in the anterior vermis. Consistent with early preferential loss of zebrin II/EAAT4-negative PCs in the vermis, the densities of microglia and the Bergmann glial expression of metallothionein I/II and the hyaluronan receptor CD44 were higher in zebrin II/EAAT4-negative zones. In contrast, early loss in lateral cerebellar lobules did not reflect a similar discrimination between PC phenotypes. Patterns of vermal PC loss became more heterogeneous at PND42, with the loss of both zebrin II/EAAT4-negative and zebrin II/EAAT4-positive neurons. At PND84, zebrin II/EAAT4 patterning was abolished in the anterior cerebellum, with preferential PC survival in lobule X. Our investigation reveals regional discrimination between patterns of PC subset loss, defined by zebrin II/EAAT4 expression domains, following neonatal viral infection. These findings suggest a differential vulnerability of PC subsets during the early stages of virus-induced neurodegeneration.

APA, Harvard, Vancouver, ISO, and other styles

10

Machtens, Jan-Philipp, Peter Kovermann, and Christoph Fahlke. "Substrate-dependent Gating of Anion Channels Associated with Excitatory Amino Acid Transporter 4." Journal of Biological Chemistry 286, no. 27 (2011): 23780–88. http://dx.doi.org/10.1074/jbc.m110.207514.

Full text

Abstract:

EAAT glutamate transporters do not only function as secondary-active glutamate transporters but also as anion channels. EAAT anion channel activity depends on transport substrates. For most isoforms, it is negligible without external Na+ and increased by external glutamate. We here investigated gating of EAAT4 anion channels with various cations and amino acid substrates using patch clamp experiments on a mammalian cell line. We demonstrate that Li+ can substitute for Na+ in supporting substrate-activated anion currents, albeit with changed voltage dependence. Anion currents were recorded in glutamate, aspartate, and cysteine, and distinct time and voltage dependences were observed. For each substrate, gating was different in external Na+ or Li+. All features of voltage-dependent and substrate-specific anion channel gating can be described by a simplified nine-state model of the transport cycle in which only amino acid substrate-bound states assume high anion channel open probabilities. The kinetic scheme suggests that the substrate dependence of channel gating is exclusively caused by differences in substrate association and translocation. Moreover, the voltage dependence of anion channel gating arises predominantly from electrogenic cation binding and membrane translocation of the transporter. We conclude that all voltage- and substrate-dependent conformational changes of the EAAT4 anion channel are linked to transitions within the transport cycle.

APA, Harvard, Vancouver, ISO, and other styles

11

FYK-KOLODZIEJ, BOZENA, PU QIN, ARTURIK DZHAGARYAN, and ROBERTA G. POURCHO. "Differential cellular and subcellular distribution of glutamate transporters in the cat retina." Visual Neuroscience 21, no. 4 (2004): 551–65. http://dx.doi.org/10.1017/s0952523804214067.

Full text

Abstract:

Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Müller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1α localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.

APA, Harvard, Vancouver, ISO, and other styles

12

Almilaji, Ahmad, Carlos Munoz, Tatsiana Pakladok, et al. "Klotho Sensitivity of the Neuronal Excitatory Amino Acid Transporters EAAT3 and EAAT4." PLoS ONE 8, no. 7 (2013): e70988. http://dx.doi.org/10.1371/journal.pone.0070988.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Burckhardt, Birgitta C., and Gerhard Burckhardt. "Interaction of Excitatory Amino Acid Transporters 1 – 3 (EAAT1, EAAT2, EAAT3) with N-Carbamoylglutamate and N-Acetylglutamate." Cellular Physiology and Biochemistry 43, no. 5 (2017): 1907–16. http://dx.doi.org/10.1159/000484110.

Full text

Abstract:

Background/Aims: Inborn deficiency of the N-acetylglutamate synthase (NAGS) impairs the urea cycle and causes neurotoxic hyperammonemia. Oral administration of N-carbamoylglutamate (NCG), a synthetic analog of N-acetylglutamate (NAG), successfully decreases plasma ammonia levels in the affected children. Due to structural similarities to glutamate, NCG may be absorbed in the intestine and taken up into the liver by excitatory amino acid transporters (EAATs). Methods: Using Xenopus laevis oocytes expressing either human EAAT1, 2, or 3, or human sodium-dependent dicarboxylate transporter 3 (NaDC3), transport-associated currents of NAG, NCG, and related dicarboxylates were assayed. Results: L-aspartate and L-glutamate produced saturable inward currents with Km values below 30 µM. Whereas NCG induced a small inward current only in EAAT3 expressing oocytes, NAG was accepted by all EAATs. With EAAT3, the NAG-induced current was sodium-dependent and saturable (Km 409 µM). Oxaloacetate was found as an additional substrate of EAAT3. In NaDC3-expressing oocytes, all dicarboxylates induced much larger inward currents than did L-aspartate and L-glutamate. Conclusion: EAAT3 may contribute to intestinal absorption and hepatic uptake of NCG. With respect to transport of amino acids and dicarboxylates, EAAT3 and NaDC3 can complement each other.

APA, Harvard, Vancouver, ISO, and other styles

14

Zhou, Lei, Li Yang, Yu-jin Li, et al. "MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson’s Disease by Binding to AXIN1." Cellular Physiology and Biochemistry 51, no. 5 (2018): 2275–89. http://dx.doi.org/10.1159/000495872.

Full text

Abstract:

Background/Aims: Parkinson’s disease (PD) is a frequently occurring condition that resulted from the loss of midbrain neurons, which synthesize the neurotransmitter dopamine. In this study, we established mouse models of PD to investigate the expression of microRNA-128 (miR-128) and mechanism through which it affects apoptosis of dopamine (DA) neurons and the expression of excitatory amino acid transporter 4 (EAAT4) via binding to axis inhibition protein 1 (AXIN1). Methods: Gene expression microarray analysis was performed to screen differentially expressed miRNAs that are associated with PD. The targeting relationship between miR-128 and AXIN1 was verified via a bioinformatics prediction and dual-luciferase reporter gene assay. After separation, DA neurons were subjected to a series of inhibitors, activators and shRNAs to validate the mechanisms of miR-128 in controlling of AXIN1 in PD. Positive protein expression of AXIN1 and EAAT4 in DA neurons was determined using immunocytochemistry. miR-128 expression and the mRNA and protein levels of AXIN1 and EAAT4 were evaluated via RT-qPCR and Western blot analysis, respectively. DA neuron apoptosis was evaluated using TUNEL staining. Results: We identified AXIN1 as an upregulated gene in PD based on the microarray data of GSE7621. AXIN1 was targeted and negatively mediated by miR-128. In the DA neurons, upregulated miR-128 expression or sh-AXIN1 increased the positive expression rate of EAAT4 together with mRNA and protein levels, but decreased the mRNA and protein levels of AXIN1, apoptosis rate along with the positive expression rate of AXIN1; however, the opposite trend was found in response to transfection with miR-128 inhibitors. Conclusion: Evidence from experimental models revealed that miR-128 might reduce apoptosis of DA neurons while increasing the expression of EAAT4 which might be related to the downregulation of AXIN1. Thus, miR-128 may serve as a potential target for the treatment of PD.

APA, Harvard, Vancouver, ISO, and other styles

15

Zhang, Dong, Shu Xu, Yiting Wang, Peng Bin, and Guoqiang Zhu. "The Amino Acid-mTORC1 Pathway Mediates APEC TW-XM-Induced Inflammation in bEnd.3 Cells." International Journal of Molecular Sciences 22, no. 17 (2021): 9245. http://dx.doi.org/10.3390/ijms22179245.

Full text

Abstract:

The blood–brain barrier (BBB) is key to establishing and maintaining homeostasis in the central nervous system (CNS); meningitis bacterial infection can disrupt the integrity of BBB by inducing an inflammatory response. The changes in the cerebral uptake of amino acids may contribute to inflammatory response during infection and were accompanied by high expression of amino acid transporters leading to increased amino acid uptake. However, it is unclear whether amino acid uptake is changed and how to affect inflammatory responses in mouse brain microvascular endothelial (bEnd.3) cells in response to Avian Pathogenic Escherichia coli TW-XM (APEC XM) infection. Here, we firstly found that APEC XM infection could induce serine (Ser) and glutamate (Glu) transport from extracellular into intracellular in bEnd.3 cells. Meanwhile, we also shown that the expression sodium-dependent neutral amino acid transporter 2 (SNAT2) for Ser and excitatory amino acid transporter 4 (EAAT4) for Glu was also significantly elevated during infection. Then, in amino acid deficiency or supplementation medium, we found that Ser or Glu transport were involving in increasing SNAT2 or EAAT4 expression, mTORC1 (mechanistic target of rapamycin complex 1) activation and inflammation, respectively. Of note, Ser or Glu transport were inhibited after SNAT2 silencing or EAAT4 silencing, resulting in inhibition of mTORC1 pathway activation, and inflammation compared with the APEC XM infection group. Moreover, pEGFP-SNAT2 overexpression and pEGFP-EAAT4 overexpression in bEnd.3 cells all could promote amino acid uptake, activation of the mTORC1 pathway and inflammation during infection. We further found mTORC1 silencing could inhibit inflammation, the expression of SNAT2 and EAAT4, and amino acid uptake. Taken together, our results demonstrated that APEC TW-XM infection can induce Ser or Glu uptake depending on amino acid transporters transportation, and then activate amino acid-mTORC1 pathway to induce inflammation in bEnd.3 cells.

APA, Harvard, Vancouver, ISO, and other styles

16

Fairman, W. A., and S. G. Amara. "Functional diversity of excitatory amino acid transporters: ion channel and transport modes." American Journal of Physiology-Renal Physiology 277, no. 4 (1999): F481—F486. http://dx.doi.org/10.1152/ajprenal.1999.277.4.f481.

Full text

Abstract:

Recent studies of glutamate transporters in the central nervous system indicate that in addition to their fundamental role in mediating neurotransmitter uptake, these proteins may contribute to the modulation of a variety of cellular processes. Activation of the excitatory amino acid (EAA) carriers generates an electrogenic current attibutable to ion-coupled cotransport. In addition to this transport-associated current, a substrate-gated thermodynamically uncoupled anion flux has been identified that has been proposed to dampen neuronal excitability. Arachidonic acid has been reported to modulate a variety of membrane proteins involved in cellular signaling. Here we discuss recent findings that indicate arachidonic acid stimulates a previously uncharacterized proton-selective conductance in the Purkinje cell-specific subtype, EAAT4. The unique channel-like porperties of the EAATs, their unexpected localization, and physiological evidence propose a modulatory role for the EAATs in neuronal signaling and suggest a broader role for glutamate transporters than simply the clearance of synaptically released glutamate. Thus, the identification of this arachidonate-stimulated proton conductance extends the complexity of mechanisms through which glutamate transporters modulate neuronal excitability.

APA, Harvard, Vancouver, ISO, and other styles

17

Shigeri, Yasushi, Keiko Shimamoto, Yoshimi Yasuda-Kamatani та ін. "Effects of threo-β-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5)". Journal of Neurochemistry 79, № 2 (2008): 297–302. http://dx.doi.org/10.1046/j.1471-4159.2001.00588.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Dalet, Antoine, Jérémie Bonsacquet, Sophie Gaboyard-Niay, et al. "Glutamate Transporters EAAT4 and EAAT5 Are Expressed in Vestibular Hair Cells and Calyx Endings." PLoS ONE 7, no. 9 (2012): e46261. http://dx.doi.org/10.1371/journal.pone.0046261.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Torres-Salazar, D., and C. Fahlke. "Intersubunit Interactions in EAAT4 Glutamate Transporters." Journal of Neuroscience 26, no. 28 (2006): 7513–22. http://dx.doi.org/10.1523/jneurosci.4545-05.2006.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Li, Liaoliao, and Zhiyi Zuo. "Glutamate Transporter Type 3 Knockout Reduces Brain Tolerance to Focal Brain Ischemia in MICE." Journal of Cerebral Blood Flow & Metabolism 31, no. 5 (2010): 1283–92. http://dx.doi.org/10.1038/jcbfm.2010.222.

Full text

Abstract:

Excitatory amino-acid transporters (EAATs) transport glutamate into cells under physiologic conditions. Excitatory amino-acid transporter type 3 (EAAT3) is the major neuronal EAAT and also uptakes cysteine, the rate-limiting substrate for synthesis of glutathione. Thus, we hypothesize that EAAT3 contributes to providing brain ischemic tolerance. Male 8-week-old EAAT3 knockout mice on CD-1 mouse gene background and wild-type CD-1 mice were subjected to right middle cerebral artery occlusion for 90 minutes. Their brain infarct volumes, neurologic functions, and brain levels of glutathione, nitrotyrosine, and 4-hydroxy-2-nonenal (HNE) were evaluated. The EAAT3 knockout mice had bigger brain infarct volumes and worse neurologic deficit scores and motor coordination functions than did wild-type mice, no matter whether these neurologic outcome parameters were evaluated at 24 hours or at 4 weeks after brain ischemia. The EAAT3 knockout mice contained higher levels of HNE in the ischemic penumbral cortex and in the nonischemic cerebral cortex than did wild-type mice. Glutathione levels in the ischemic and nonischemic cortices of EAAT3 knockout mice tended to be lower than those of wild-type mice. Our results suggest that EAAT3 is important in limiting ischemic brain injury after focal brain ischemia. This effect may involve attenuating brain oxidative stress.

APA, Harvard, Vancouver, ISO, and other styles

21

Cater, Rosemary J., Robert J. Vandenberg, and Renae M. Ryan. "Tuning the ion selectivity of glutamate transporter–associated uncoupled conductances." Journal of General Physiology 148, no. 1 (2016): 13–24. http://dx.doi.org/10.1085/jgp.201511556.

Full text

Abstract:

The concentration of glutamate within a glutamatergic synapse is tightly regulated by excitatory amino acid transporters (EAATs). In addition to their primary role in clearing extracellular glutamate, the EAATs also possess a thermodynamically uncoupled Cl− conductance. This conductance is activated by the binding of substrate and Na+, but the direction of Cl− flux is independent of the rate or direction of substrate transport; thus, the two processes are thermodynamically uncoupled. A recent molecular dynamics study of the archaeal EAAT homologue GltPh (an aspartate transporter from Pyrococcus horikoshii) identified an aqueous pore at the interface of the transport and trimerization domains, through which anions could permeate, and it was suggested that an arginine residue at the most restricted part of this pathway might play a role in determining anion selectivity. In this study, we mutate this arginine to a histidine in the human glutamate transporter EAAT1 and investigate the role of the protonation state of this residue on anion selectivity and transporter function. Our results demonstrate that a positive charge at this position is crucial for determining anion versus cation selectivity of the uncoupled conductance of EAAT1. In addition, because the nature of this residue influences the turnover rate of EAAT1, we reveal an intrinsic link between the elevator movement of the transport domain and the Cl− channel.

APA, Harvard, Vancouver, ISO, and other styles

22

Todd, Alison C., and Giles E. Hardingham. "The Regulation of Astrocytic Glutamate Transporters in Health and Neurodegenerative Diseases." International Journal of Molecular Sciences 21, no. 24 (2020): 9607. http://dx.doi.org/10.3390/ijms21249607.

Full text

Abstract:

The astrocytic glutamate transporters excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2) play a key role in nervous system function to maintain extracellular glutamate levels at low levels. In physiology, this is essential for the rapid uptake of synaptically released glutamate, maintaining the temporal fidelity of synaptic transmission. However, EAAT1/2 hypo-expression or hypo-function are implicated in several disorders, including epilepsy and neurodegenerative diseases, as well as being observed naturally with aging. This not only disrupts synaptic information transmission, but in extremis leads to extracellular glutamate accumulation and excitotoxicity. A key facet of EAAT1/2 expression in astrocytes is a requirement for signals from other brain cell types in order to maintain their expression. Recent evidence has shown a prominent role for contact-dependent neuron-to-astrocyte and/or endothelial cell-to-astrocyte Notch signalling for inducing and maintaining the expression of these astrocytic glutamate transporters. The relevance of this non-cell-autonomous dependence to age- and neurodegenerative disease-associated decline in astrocytic EAAT expression is discussed, plus the implications for disease progression and putative therapeutic strategies.

APA, Harvard, Vancouver, ISO, and other styles

23

Mordrelle, Agnès, Eric Jullian, Cyrille Costa, et al. "EAAT1 is involved in transport ofl-glutamate during differentiation of the Caco-2 cell line." American Journal of Physiology-Gastrointestinal and Liver Physiology 279, no. 2 (2000): G366—G373. http://dx.doi.org/10.1152/ajpgi.2000.279.2.g366.

Full text

Abstract:

Little is known concerning the expression of amino acid transporters during intestinal epithelial cell differentiation. The transport mechanism ofl-glutamate and its regulation during the differentiation process were investigated using the human intestinal Caco-2 cell line. Kinetic studies demonstrated the presence of a single, high-affinity,d-aspartate-sensitive l-glutamate transport system in both confluent and fully differentiated Caco-2 cells. This transport was clearly Na+ dependent, with a Hill coefficient of 2.9 ± 0.3, suggesting a 3 Na+-to-1 glutamate stoichiometry and corresponding to the well-characterized XA,G − system. The excitatory amino acid transporter (EAAT)1 transcript was consistently expressed in the Caco-2 cell line, whereas the epithelial and neuronal EAAT3 transporter was barely detected. In contrast with systems B0 and y+, which have previously been reported to be downregulated when Caco-2 cells stop proliferating, l-glutamate transport capacity was found to increase steadily between day 8 and day 17. This increase was correlated with the level of EAAT1 mRNA, which might reflect an increase in EAAT1 gene transcription and/or stabilization of the EAAT1 transcript.

APA, Harvard, Vancouver, ISO, and other styles

24

Hu, Wen-Hui, Winston M. Walters, Xiao-Mei Xia, Shaffiat A. Karmally, and John R. Bethea. "Neuronal glutamate transporter EAAT4 is expressed in astrocytes." Glia 44, no. 1 (2003): 13–25. http://dx.doi.org/10.1002/glia.10268.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Alesutan, Ioana, Oana Ureche, Joerg Laufer, et al. "Regulation of the Glutamate Transporter EAAT4 by PIKfyve." Cellular Physiology and Biochemistry 25, no. 2-3 (2010): 187–94. http://dx.doi.org/10.1159/000276569.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Kolen, Bettina, Daniel Kortzak, Arne Franzen, and Christoph Fahlke. "An amino-terminal point mutation increases EAAT2 anion currents without affecting glutamate transport rates." Journal of Biological Chemistry 295, no. 44 (2020): 14936–47. http://dx.doi.org/10.1074/jbc.ra120.013704.

Full text

Abstract:

Excitatory amino acid transporters (EAATs) are prototypical dual function proteins that function as coupled glutamate/Na+/H+/K+ transporters and as anion-selective channels. Both transport functions are intimately intertwined at the structural level: Secondary active glutamate transport is based on elevator-like movements of the mobile transport domain across the membrane, and the lateral movement of this domain results in anion channel opening. This particular anion channel gating mechanism predicts the existence of mutant transporters with changed anion channel properties, but without alteration in glutamate transport. We here report that the L46P mutation in the human EAAT2 transporter fulfills this prediction. L46 is a pore-forming residue of the EAAT2 anion channels at the cytoplasmic entrance into the ion conduction pathway. In whole-cell patch clamp recordings, we observed larger macroscopic anion current amplitudes for L46P than for WT EAAT2. Rapid l-glutamate application under forward transport conditions demonstrated that L46P does not reduce the transport rate of individual transporters. In contrast, changes in selectivity made gluconate permeant in L46P EAAT2, and nonstationary noise analysis revealed slightly increased unitary current amplitudes in mutant EAAT2 anion channels. We used unitary current amplitudes and individual transport rates to quantify absolute open probabilities of EAAT2 anion channels from ratios of anion currents by glutamate uptake currents. This analysis revealed up to 7-fold increased absolute open probability of L46P EAAT2 anion channels. Our results reveal an important determinant of the diameter of EAAT2 anion pore and demonstrate the existence of anion channel gating processes outside the EAAT uptake cycle.

APA, Harvard, Vancouver, ISO, and other styles

27

Matthews, James C., Mark J. Beveridge, Marc S. Malandro, et al. "Activity and protein localization of multiple glutamate transporters in gestation day 14 vs. day 20 rat placenta." American Journal of Physiology-Cell Physiology 274, no. 3 (1998): C603—C614. http://dx.doi.org/10.1152/ajpcell.1998.274.3.c603.

Full text

Abstract:

Concentrative absorption of glutamate by the developing placenta is critical for proper fetal development. The expression of GLAST1, GLT1, EAAC1, and EAAT4, known to be capable ofd-aspartate-inhibitable and Na+-coupled glutamate transport (system [Formula: see text]), was evaluated in day 14 vs. day 20 rat chorioallantoic placenta. Steady-state mRNA levels were greater at day 20 for all transporters. Immunohistochemistry determined that the expression of GLAST1, GLT1, and EAAC1 was greater throughout the day 20 placenta and was asymmetric with respect to cellular localization. EAAT4 protein was not detected. System[Formula: see text] activity was responsible for most of the Na+-dependent glutamate uptake and was greater in day 20 than in day 14apical and basal membrane subdomains of the labyrinth syncytiotrophoblast. Greater quantities of EAAC1 and GLAST1 protein were identified on day 20, and quantities were greater in basal than in apical membranes. GLT1 expression, unchanged in apical membranes, was decreased in basal membranes. These data correlate transporter mRNA and protein content with transport activity and demonstrate an increasing capacity for glutamate absorption by the developing placenta.

APA, Harvard, Vancouver, ISO, and other styles

28

Zink, M., B. Vollmayr, P. J. Gebicke-Haerter, and F. A. Henn. "Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression." Neuropharmacology 58, no. 2 (2010): 465–73. http://dx.doi.org/10.1016/j.neuropharm.2009.09.005.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

O'Kane, Robyn L., Itziar Martı́nez-López, Mary R. DeJoseph, Juan R. Viña, and Richard A. Hawkins. "Na+-dependent Glutamate Transporters (EAAT1, EAAT2, and EAAT3) of the Blood-Brain Barrier." Journal of Biological Chemistry 274, no. 45 (1999): 31891–95. http://dx.doi.org/10.1074/jbc.274.45.31891.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Mitrovic, Ann D., Fiona Plesko, and Robert J. Vandenberg. "Zn2+Inhibits the Anion Conductance of the Glutamate Transporter EAAT4." Journal of Biological Chemistry 276, no. 28 (2001): 26071–76. http://dx.doi.org/10.1074/jbc.m011318200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Yamashita, Akihide, Koshi Makita, Toshihiko Kuroiwa, and Kohichi Tanaka. "Glutamate transporters GLAST and EAAT4 regulate postischemic Purkinje cell death: An in vivo study using a cardiac arrest model in mice lacking GLAST or EAAT4." Neuroscience Research 55, no. 3 (2006): 264–70. http://dx.doi.org/10.1016/j.neures.2006.03.007.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Matott, Michael P., Brian C. Ruyle, Eileen M. Hasser, and David D. Kline. "Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function." Journal of Neurophysiology 115, no. 3 (2016): 1691–702. http://dx.doi.org/10.1152/jn.01054.2015.

Full text

Abstract:

The nucleus tractus solitarii (nTS) is the initial central termination site for visceral afferents and is important for modulation and integration of multiple reflexes including cardiorespiratory reflexes. Glutamate is the primary excitatory neurotransmitter in the nTS and is removed from the extracellular milieu by excitatory amino acid transporters (EAATs). The goal of this study was to elucidate the role of EAATs in the nTS on basal synaptic and neuronal function and cardiorespiratory regulation. The majority of glutamate clearance in the central nervous system is believed to be mediated by astrocytic EAAT 1 and 2. We confirmed the presence of EAAT 1 and 2 within the nTS and their colocalization with astrocytic markers. EAAT blockade with dl- threo-β-benzyloxyaspartic acid (TBOA) produced a concentration-related depolarization, increased spontaneous excitatory postsynaptic current (EPSC) frequency, and enhanced action potential discharge in nTS neurons. Solitary tract-evoked EPSCs were significantly reduced by EAAT blockade. Microinjection of TBOA into the nTS of anesthetized rats induced apneic, sympathoinhibitory, depressor, and bradycardic responses. These effects mimicked the response to microinjection of exogenous glutamate, and glutamate responses were enhanced by EAAT blockade. Together these data indicate that EAATs tonically restrain nTS excitability to modulate cardiorespiratory function.

APA, Harvard, Vancouver, ISO, and other styles

33

Lin, Chien-Liang Glenn, Anastassios V. Tzingounis, Lin Jin, Akiko Furuta, Michael P. Kavanaugh, and Jeffrey D. Rothstein. "Molecular cloning and expression of the rat EAAT4 glutamate transporter subtype." Molecular Brain Research 63, no. 1 (1998): 174–79. http://dx.doi.org/10.1016/s0169-328x(98)00256-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

34

Jackson, Mandy, Wei Song, Mu-Ya Liu, et al. "Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins." Nature 410, no. 6824 (2001): 89–93. http://dx.doi.org/10.1038/35065091.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Yamada, Keiko, Masahiko Watanabe, Takashi Shibata, Kohichi Tanaka, Keiji Wada, and Yoshiro Inoue. "EAAT4 is a post-synaptic glutamate transporter at Purkinje cell synapses." NeuroReport 7, no. 12 (1996): 2013–17. http://dx.doi.org/10.1097/00001756-199608120-00032.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Kovermann, Peter A., and Christoph Fahlke. "Voltage-dependent Gating Of Wt And D177a Eaat4-associated Anion Channels." Biophysical Journal 96, no. 3 (2009): 472a. http://dx.doi.org/10.1016/j.bpj.2008.12.2429.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Rimaniol, Anne-Cécile, Patricia Mialocq, Pascal Clayette, Dominique Dormont, and Gabriel Gras. "Role of glutamate transporters in the regulation of glutathione levels in human macrophages." American Journal of Physiology-Cell Physiology 281, no. 6 (2001): C1964—C1970. http://dx.doi.org/10.1152/ajpcell.2001.281.6.c1964.

Full text

Abstract:

Cysteine is the limiting precursor for glutathione synthesis. Because of its low bioavailability, cysteine is generally produced from cystine, which may be taken up through two different transporters. The cystine/glutamate antiporter (x[Formula: see text] system) transports extracellular cystine in exchange for intracellular glutamate. The XAG transport system takes up extracellular cystine, glutamate, and aspartate. Both are sensitive to competition between cystine and glutamate, and excess extracellular glutamate thus inhibits glutathione synthesis, a nonexcitotoxic mechanism for glutamate toxicity. We demonstrated previously that human macrophages express the glutamate transporters excitatory amino acid transporter (EAAT)1 and EAAT2 (which do not transport cystine, X[Formula: see text] system) and overcome competition for the use of cystine transporters. We now show that macrophages take up cystine through the x[Formula: see text] and not the XAG system. We also found that glutamate, although competing with cystine uptake, dose-dependently increases glutathione synthesis. We used inhibitors to demonstrate that this increase is mediated by EAATs. EAAT expression in macrophages thus leads to glutamate-dependent enhancement of glutathione synthesis by providing intracellular glutamate for direct insertion in glutathione and also for fueling the intracellular pool of glutamate and trans-stimulating the cystine/glutamate antiporter.

APA, Harvard, Vancouver, ISO, and other styles

38

Tanaka, Jun, Keiko Yamada, Masahiko Watanabe, Koichii Tanaka, Keiji Wada, and Yoshiro Inoue. "910 Extrasynaptic localization of the glutamate transport EAAT4 at Purkinje cell synapses." Neuroscience Research 28 (January 1997): S113. http://dx.doi.org/10.1016/s0168-0102(97)90300-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Itoh, Masayuki, Yukiko Watanabe, Masahiko Watanabe, Kohichi Tanaka, Keiji Wada, and Sachio Takashima. "Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum." Brain Research 767, no. 2 (1997): 265–71. http://dx.doi.org/10.1016/s0006-8993(97)00572-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Massie, Ann, Frans Vandesande, and Lutgarde Arckens. "Expression of the high-affinity glutamate transporter EAAT4 in mammalian cerebral cortex." Neuroreport 12, no. 2 (2001): 393–97. http://dx.doi.org/10.1097/00001756-200102120-00041.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Tanaka, Jun, Ryoichi Ichikawa, Masahiko Watanabe, Kohichi Tanaka, and Yoshiro Inoue. "Extra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses." NeuroReport 8, no. 11 (1997): 2461–64. http://dx.doi.org/10.1097/00001756-199707280-00010.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Tzingounis, Anastassios V., Chien-Liang Lin, Jeffrey D. Rothstein, and Michael P. Kavanaugh. "Arachidonic Acid Activates a Proton Current in the Rat Glutamate Transporter EAAT4." Journal of Biological Chemistry 273, no. 28 (1998): 17315–17. http://dx.doi.org/10.1074/jbc.273.28.17315.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Miralles, Vicente J., Itziar Martı́nez-López, Rosa Zaragozá, et al. "Na+ dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) in primary astrocyte cultures: effect of oxidative stress." Brain Research 922, no. 1 (2001): 21–29. http://dx.doi.org/10.1016/s0006-8993(01)03124-9.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Yukitake, Motohiro, Jun-ichi Satoh, Shigeru Katamine, and Yasuo Kuroda. "EAAT4 mRNA expression is preserved in the cerebellum of prion protein-deficient mice." Neuroscience Letters 352, no. 3 (2003): 171–74. http://dx.doi.org/10.1016/j.neulet.2003.08.057.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Poulsen, Miguel V., and Robert J. Vandenberg. "Niflumic acid modulates uncoupled substrate‐gated conductances in the human glutamate transporter EAAT4." Journal of Physiology 534, no. 1 (2001): 159–67. http://dx.doi.org/10.1111/j.1469-7793.2001.00159.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Böhmer, Christoph, Michaele Philippin, Jeyaganesh Rajamanickam, et al. "Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and PKB." Biochemical and Biophysical Research Communications 324, no. 4 (2004): 1242–48. http://dx.doi.org/10.1016/j.bbrc.2004.09.193.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Huang, Y. H. "Climbing Fiber Activation of EAAT4 Transporters and Kainate Receptors in Cerebellar Purkinje Cells." Journal of Neuroscience 24, no. 1 (2004): 103–11. http://dx.doi.org/10.1523/jneurosci.4473-03.2004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Damm-Ganamet, Kelly L., Marie-Laure Rives, Alan D. Wickenden, Heather M. McAllister, and Taraneh Mirzadegan. "A computational approach yields selective inhibitors of human excitatory amino acid transporter 2 (EAAT2)." Journal of Biological Chemistry 295, no. 13 (2020): 4359–66. http://dx.doi.org/10.1074/jbc.ac119.011190.

Full text

Abstract:

Excitatory amino acid transporters (EAATs) represent a protein family that is an emerging drug target with great therapeutic potential for managing central nervous system disorders characterized by dysregulation of glutamatergic neurotransmission. As such, it is of significant interest to discover selective modulators of EAAT2 function. Here, we applied computational methods to identify specific EAAT2 inhibitors. Utilizing a homology model of human EAAT2, we identified a binding pocket at the interface of the transport and trimerization domain. We next conducted a high-throughput virtual screen against this site and identified a selective class of EAAT2 inhibitors that were tested in glutamate uptake and whole-cell electrophysiology assays. These compounds represent potentially useful pharmacological tools suitable for further exploration of the therapeutic potential of EAAT2 and may provide molecular insights into mechanisms of allosteric modulation for glutamate transporters.

APA, Harvard, Vancouver, ISO, and other styles

49

Martinez, Diana, Richard C. Rogers, Eileen M. Hasser, Gerlinda E. Hermann, and David D. Kline. "Loss of excitatory amino acid transporter restraint following chronic intermittent hypoxia contributes to synaptic alterations in nucleus tractus solitarii." Journal of Neurophysiology 123, no. 6 (2020): 2122–35. http://dx.doi.org/10.1152/jn.00766.2019.

Full text

Abstract:

Removal of excitatory amino acid transporter (EAAT) restraint increases spontaneous synaptic activity yet decreases afferent [tractus solitarii (TS)]-driven excitatory postsynaptic current (EPSC) amplitude. In the chronic intermittent hypoxia model of obstructive sleep apnea, this restraint is lost due to reduction in EAAT expression and function. Thus EAATs are important in controlling elevated glutamatergic signaling, and loss of such control results in maladaptive synaptic signaling.

APA, Harvard, Vancouver, ISO, and other styles

50

Fairman, Wendy A., Mark S. Sonders, Geoffrey H. Murdoch, and Susan G. Amara. "Arachidonic acid elicits a substrate-gated proton current associated with the glutamate transporter EAAT4." Nature Neuroscience 1, no. 2 (1998): 105–13. http://dx.doi.org/10.1038/355.

Full text

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!