ライフサイエンスコーパス: EAAT2

1 of the excitatory amino acid transporter 2 (EAAT2) .

2 , the ortholog of mammalian astrocytic GLT1 (EAAT2).

3 of the excitatory amino acid transporter 2 (EAAT2).

4 mate, via neurotransmitter transport by GLT1/EAAT2.

5 s in the necrotic foci in PVL also expressed EAAT2.

6 predominant forebrain glutamate transporter, EAAT2.

7 gate IKKbeta- and p65-mediated activation of EAAT2.

8 its both basal and p65-induced activation of EAAT2.

9 ding to a 59- and 45-fold selectivity toward EAAT2.

10 port is handled by the glutamate transporter EAAT2.

11 in the promoter of rat Slc1a2 gene encoding EAAT2.

12 HNE was the astrocytic glutamate transporter EAAT2.

13 glial specific glutamate transporter protein EAAT2.

14 GLT-1 and excitatory amino acid transporter EAAT2.

15 her suggest the presence of a sodium leak in EAAT2.

16 n, we synthesized novel activators (4a-f) of EAAT2.

17 tumor necrosis factor alpha (TNF-alpha), on EAAT2.

18 tatory amino-acid transporter 1 (EAAT1), and EAAT2.

19 uptake and heteroexchange are comparable in EAAT2.

20 and attenuated the Mn-induced repression of EAAT2.

21 y for the third glutamate transporter GLT-1 (EAAT2), a putatively glial transporter, in microculture

22 NA levels of the glial glutamate transporter EAAT2, a protein regulated by GRM3 that critically modul

23 te-mediated excitotoxic injury and death via EAAT2 activation.

24 LDN-212320 (3) was found to be a potent EAAT2 activator at a translational level, restoring the

25 prolongs survival, and ceftriaxone increases EAAT2 activity.

26 ggest EAAT2b transports glutamate similar to EAAT2, although the contribution of EAAT2b to normal cle

27 mains revealed that a large portion of total EAAT2 and a minor portion of total EAAT1, EAAT3, and EAA

28 EAAT2 and AQP4 colocalization was also reduced in the st

29 Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macrom

30 gesting that ENT1-mediated downregulation of EAAT2 and AQP4 expression contributes to excessive ethan

31 indicate that adenosine signaling regulates EAAT2 and astrocytic AQP4 expressions, which control eth

32 se to two fragments that we termed truncated EAAT2 and COOH terminus of EAAT2 (CTE).

33 inhibitor at EAAT1 (IC50 20 muM) compared to EAAT2 and EAAT3 (IC50 > 300 muM).

34 city of UCPH-101 and UCPH-102 for EAAT1 over EAAT2 and EAAT3 is demonstrated to extend to the EAAT4 a

35 EAAT1 with a 14- and 9-fold preference over EAAT2 and EAAT3, respectively.

36 itical negative transcriptional regulator of EAAT2 and mediates Mn-induced EAAT2 repression.

37 r Yin Yang 1 (YY1) is critical in repressing EAAT2 and mediates the effects of negative regulators, s

38 st that NF-kappaB can intrinsically activate EAAT2 and that TNFalpha mediates repression through a di

39 e to generate transgenic mice overexpressing EAAT2 and then to cross these mice with the ALS-associat

40 plasmalemmal glial-glutamate transporter 2 (EAAT2) and increased vesicular glutamate transporter-1 (

41 for glutamate exist on astrocytes (EAAT1 and EAAT2) and neurons (EAAT3).

42 xpression of the glutamate transporter Glt1 (EAAT2) and protects these animals from death.

43 of type 2 excitatory amino-acid transporter (EAAT2) and the astrocyte-specific water channel, aquapor

44 romoter of astroglial glutamate transporter (EAAT2) and the same approach was initially used here to

45 ased glutamate uptake, a primary function of EAAT2, and EAAT2 small interference RNA completely inhib

46 cDNA for EAAT1, EAAT2, and EAAT3 was observed, indicating that mRNA was

47 ry amino acid transporter transcripts EAAT1, EAAT2, and EAAT3 was performed in discrete thalamic nucl

48 s found to be approximately 1:3:6 for EAAT1, EAAT2, and EAAT3, respectively.

49 nst the full-length coding regions of EAAT1, EAAT2, and EAAT3.

50 atory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3.

51 er (DAT) and the glial glutamate transporter EAAT2, and we identified a conserved serine residue in F

52 and impairment in expression and activity of EAAT2 are two distinct molecular mechanisms occurring in

53 that the glutamate transporters, especially EAAT2, are associated with cholesterol-rich lipid raft m

54 it EAAT2 by triggering caspase-3 cleavage of EAAT2 at a single defined locus.

55 rt the novel evidence that caspase-3 cleaves EAAT2 at a unique site located in the cytosolic C-termin

56 EAAT2 block also augmented action potential discharge in

57 Astrocytic EAAT2 buffers basal glutamate activation of AMPA-type gl

58 2 expression and function, elevated not only EAAT2 but also AQP4 expression in the striatum.

59 xpressions of transcripts encoding EAAT1 and EAAT2, but not EAAT3, were detected in the thalamus of s

60 proteins exposed to oxidative stress inhibit EAAT2 by triggering caspase-3 cleavage of EAAT2 at a sin

61 Using EAAT2 constructs with an extracellular biotin acceptor t

62 ism by which the glial glutamate transporter EAAT2 could contribute to the pathology of ALS.

63 The loss of functional EAAT2 could lead to the accumulation of extracellular gl

64 termed truncated EAAT2 and COOH terminus of EAAT2 (CTE).

65 mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeo

66 Since glutamate toxicity caused by EAAT2 dysfunction is thought to promote several differen

67 imal and human tissue: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5.

68 have been identified in human brain: EAAT1, EAAT2, EAAT3, and EAAT4.

69 d analogous effects on GltPh simulations and EAAT2/EAAT4 measurements of single-channel currents and

70 edominant astroglial L-glutamate transporter EAAT2 (excitatory amino acid transporter 2) does not con

71 EAAT2 (excitatory amino acid transporter 2) is a high af

72 loss of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2) protein in m

73 ne, an antibiotic compound known to increase EAAT2 expression and function, elevated not only EAAT2 b

74 ain constant, indicating that alterations in EAAT2 expression are due to disturbances at the post-tra

75 ndicate that strategies designed to increase EAAT2 expression have potential for preventing excitotox

76 Despite the lower level of EAAT2 expression in glutamatergic terminals, when hippoc

77 mmunohistochemistry confirmed an increase in EAAT2 expression in hippocampus, identifying a possible

78 the mechanism by which ceftriaxone enhances EAAT2 expression in primary human fetal astrocytes (PHFA

79 cell- and region-level studies of EAAT1 and EAAT2 expression in the mediodorsal nucleus of the thala

80 The regulation of EAAT2 expression involves actin polymerization-dependent

81 Previously, we found that EAAT2 expression is limited primarily to premyelinating

82 Increased EAAT2 expression protects neurons from L-glutamate induc

83 ed repression and EGF-mediated activation of EAAT2 expression require NF-kappaB.

84 veral classes of compounds that can increase EAAT2 expression through translational activation.

85 beta-lactam antibiotics, is a stimulator of EAAT2 expression with neuroprotective effects in both in

86 that transcriptional processes can regulate EAAT2 expression.

87 remature death, confirming the importance of EAAT2 for brain function and validating the genetic cons

88 ibition of GLT-1 [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with dihy

89 tin-cyclization recombinase (Cre) eliminated EAAT2 from the brain, resulting in epilepsy and prematur

90 Reduced EAAT2 function could lead to accumulation of extracellul

91 otential tool for the further elucidation of EAAT2 function.

92 sporter studies demonstrated a large loss of EAAT2 function.

93 of astrocytic glutamate transporter (GLT-1; EAAT2) function is associated with multiple neurodegener

94 Furthermore, our EAAT2/G93A double transgenic mice showed a statistically

95 haracterized the genomic organization of the EAAT2 gene and used single-strand conformation polymorph

96 dies indicate that germline mutations in the EAAT2 gene are infrequent and do not explain the presenc

97 Here we floxed the EAAT2 gene to produce the first conditional EAAT2 knock-

98 sis revealed reduced transcripts of Gad1 and Eaat2 genes, which code for enzymes involved in the synt

99 f the high-affinity glutamate transporter 1 (EAAT2/GLT-1) in the nucleus accumbens (NAc).

100 The glutamate transporter gene, EAAT2/GLT-1, is induced by epidermal growth factor (EGF)

101 Focal loss of the EAAT2 glutamate transporter in the ventral horn of the s

102 The EAAT2 glutamate transporter, accounts for >90% of hippoc

103 ion, by studying the expression of EAAT1 and EAAT2 glutamate transporters, it was possible to documen

104 lutamate from the synaptic cleft and loss of EAAT2 has been previously reported in amyotrophic latera

105 pts for the astroglial glutamate transporter EAAT2 have been detected in brain tissues of 60% of pati

106 s the most potent and selective inhibitor of EAAT2 identified to date.

107 showed a significantly higher percentage of EAAT2-immunopositive astrocytes in PVL (51.8% +/- 5.6%)

108 in vivo resulted in the formation of larger EAAT2-immunoreactive clusters on the cell surface.

109 , which appeared concurrently to the loss of EAAT2 immunoreactivity and to increased expression of ac

110 and glutamate that resembles original GLT-1/EAAT2 in all tested functional aspects.

111 These findings suggest that the loss of EAAT2 in ALS is due to aberrant mRNA and that these aber

112 Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal co

113 In this study, we analyzed the expression of EAAT2 in cerebral white matter from PVL and control case

114 t mediate TX-induced up-regulation of GLT-1 (EAAT2 in humans), we investigated its effect on GLT-1 at

115 king finding was the transient expression of EAAT2 in layer V pyramidal neuronal cell bodies up until

116 the presence of variant mRNA transcripts of EAAT2 in more than one-half of ALS cases.

117 Double-label immunocytochemistry detected EAAT2 in OLs but not astrocytes or axons in the human fe

118 blot analysis suggested an up-regulation of EAAT2 in PVL compared with control cases.

119 The expression of EAAT2 in pyramidal neurons during human brain developmen

120 The previously unrecognized up-regulation of EAAT2 in reactive astrocytes and its presence in macroph

121 ethanol withdrawal-induced downregulation of EAAT2 in the striatum.

122 sporter excitatory amino acid transporter 2 (EAAT2) in LPS-treated astrocytes.

123 ter was responsible for ceftriaxone-mediated EAAT2 induction.

124 tion and cardiorespiratory effects following EAAT2 inhibition were due to activation of putative extr

125 F3-phenyl analogue 4r was a potent selective EAAT2-inhibitor (IC50 = 2.8 muM) exhibiting 30- and 50-f

126 aluating both the stimulation of currents in EAAT2-injected oocytes and the heteroexchange of d-[(3)H

127 EAAT2 is a high affinity, Na+-dependent glutamate transp

128 ompound treatment cessation, suggesting that EAAT2 is a potential disease modifier with therapeutic p

129 Glial recordings confirmed EAAT2 is functional on nTS astrocytes.

130 Dysfunction of EAAT2 is implicated in acute and chronic neurological di

131 emonstrate that normal function of EAAT1 and EAAT2 is necessary for retinal ganglion cell survival an

132 astrocyte endocytosis of NMO-IgG, AQP4, and EAAT2 is not a significant consequence of AQP4 autoantib

133 findings suggest that caspase-3 cleavage of EAAT2 is one mechanism responsible for the impairment of

134 Although EAAT2 is predominantly expressed in astrocytes, approxim

135 The glial glutamate transporter EAAT2 is primarily responsible for clearance of glutamat

136 l of the disease, expression and activity of EAAT2 is remarkably reduced.

137 ies demonstrate that under normal conditions EAAT2 is specific to astrocytes.

138 The glial glutamate transporter EAAT2 is the main mediator of glutamate clearance.

139 Since EAAT2 is the most expressed EAAT in the nTS, this study

140 Excitotoxicity caused by down-regulation of EAAT2 is thought to be a contributing factor to motor ne

141 Excitatory amino acid transporter-2 (EAAT2) is a major glutamate transporter in the brain exp

142 POINTS: Excitatory amino acid transporter 2 (EAAT2) is present on astrocytes in the nucleus tractus s

143 t was observed using inhibitors specific for EAAT2 (kainic acid and dihydrokainic acid) and EAAT3 (cy

144 EAAT2 gene to produce the first conditional EAAT2 knock-out mice.

145 A truncated splice variant of EAAT2, known as EAAT2b, also has been identified in astr

146 QP4 and the associated glutamate transporter EAAT2, leading to glutamate excitotoxicity.

147 Caspase-3 cleavage of EAAT2 leads to a drastic and selective inhibition of thi

148 Loss of EAAT2 leads to increased extracellular glutamate and exc

149 phic lateral sclerosis motor cortex, whereas EAAT2 levels were decreased by up to 95%.

150 tochemistry, and proteome analysis) that the EAAT2 levels were too low to support any of the four hyp

151 mutant SOD1 ALS mice of a truncated form of EAAT2, likely deriving from caspase-3-mediated proteolyt

152 , we failed to detect genetic linkage to the EAAT2 locus.

153 At end-stage disease, gliosis increased and EAAT2 loss in the ventral horn exceeded 90%, suggesting

154 have tested the hypothesis that the gene for EAAT2 may be defective in some ALS cases.

155 s suggest that the dramatic abnormalities in EAAT2 may be due to translational or post-translational

156 These results suggest that the loss of EAAT2 may contribute to, but does not cause, motor neuro

157 een the distribution of EAAT2 protein and of EAAT2-mediated transport activity.

158 Glial glutamate transporter EAAT2-mediated uptake was more sensitive to this effect.

159 GLT-1 (EAAT2) mediates the bulk of this activity in forebrain.

160 EAAT2 modulates cardiorespiratory control and tempers ex

161 xpressed in astrocytes, approximately 10% of EAAT2 molecules are found in axon terminals.

162 EAAT2 mRNA levels, however, remain constant, indicating

163 Multiple EAAT2 mRNA transcripts have been described, but those re

164 EAAT2 mRNA was abundant in human fetal white matter duri

165 Multiple abnormal EAAT2 mRNAs, including intron-retention and exon-skippin

166 mportantly, this translational regulation of EAAT2 occurred in vivo (i.e. both in primary cortical ne

167 We conclude that transient expression of EAAT2 occurs during the window of peak vulnerability for

168 novo variants were found only in SLC1A2 (aka EAAT2 or GLT1) (c.244G>A [p.Gly82Arg]) and YWHAG (aka 14

169 as no quantitative change in mRNA for EAAT1, EAAT2, or EAAT3 in ALS motor cortex, even in patients wi

170 were not significantly different for EAAT1, EAAT2, or EAAT3, but 2-FAA exhibited higher affinity for

171 pressing the human transporter clones EAAT1, EAAT2, or EAAT3, it was found that the pharmacological p

172 ecreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs

173 Glial glutamate transporter EAAT2 plays a major role in glutamate clearance in synap

174 The astroglial glutamate transporter EAAT2 plays a major role in maintaining low levels of ex

175 s indicated that glial glutamate transporter EAAT2 plays an essential role in cognitive functions and

176 d new light on the important role astrocytic EAAT2 plays on buffering nTS excitation and overall card

177 transport in PHFA through NF-kappaB-mediated EAAT2 promoter activation.

178 Mn decreases EAAT2 promoter activity and mRNA and protein levels, but

179 and, accordingly, HDAC inhibitors increased EAAT2 promoter activity and reversed the Mn-induced repr

180 YY1 overexpression in astrocytes reduced EAAT2 promoter activity, while YY1 knockdown or mutation

181 ty and reversed the Mn-induced repression of EAAT2 promoter activity.

182 or mutation of the YY1 consensus site of the EAAT2 promoter increased its promoter activity and atten

183 ey raise the intriguing possibility that the EAAT2 promoter may be useful for targeting gene expressi

184 This led to increased YY1 binding to the EAAT2 promoter region.

185 ing only one of the co-inherited SNPs in the EAAT2 promoter to human diseases.

186 g.-168C > T giving a rise to a total of ten EAAT2 promoter variants.

187 paB binding site at the -272 position of the EAAT2 promoter was responsible for ceftriaxone-mediated

188 ntly, we find that N-myc is recruited to the EAAT2 promoter with TNFalpha and that N-myc-binding site

189 he cloning and characterization of the human EAAT2 promoter, demonstrating elevated expression in ast

190 leoprotein K (hnRNP K), which binds the GLT1/EAAT2 promoter.

191 ortex, even in patients with a large loss of EAAT2 protein (95% decrease compared with control) and d

192 rent study, we investigated whether restored EAAT2 protein and function could benefit cognitive funct

193 plained mismatch between the distribution of EAAT2 protein and of EAAT2-mediated transport activity.

194 We show that the amount of EAAT2 protein and the associated Na+-dependent glutamate

195 y play an important role in the differential EAAT2 protein expression under normal and disease condit

196 m both approaches demonstrated that restored EAAT2 protein function significantly improved cognitive

197 role in cognitive functions and that loss of EAAT2 protein is a common phenomenon observed in AD pati

198 These results indicate that expression of EAAT2 protein is highly regulated at the translational l

199 Transport-competent EAAT2 protein is up-regulated in differentiating astrocy

200 hic lateral sclerosis and Alzheimer disease, EAAT2 protein levels are significantly decreased in affe

201 Immunoblotting demonstrated that EAAT2 protein was highly expressed in early development

202 The transgenic EAAT2 protein was properly localized to the cell surface

203 be involved in N-linked glycosylation of the EAAT2 protein.

204 tion in excitatory amino acid transporter 2 (EAAT2) protein levels in astrocyte cultures, which was b

205 wever, RFX1 did not change the expression of EAAT2 proteins in the NRK52E cells.

206 and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol wit

207 he glutamate transporter GLT1 (also known as EAAT2; refs 1, 2), the physiologically dominant astrogli

208 Since the pharmacologic activation of EAAT2 represents a valuable strategy to relieve neuropat

209 s, but the molecular mechanism of Mn-induced EAAT2 repression at the transcriptional level has yet to

210 l regulator of EAAT2 and mediates Mn-induced EAAT2 repression.

211 produce a dominant negative effect on normal EAAT2 resulting in loss of protein and activity.

212 ecially excitatory amino acid transporter 2 (EAAT2, rodent analog GLT1) to regulate extracellular glu

213 known to increase the glutamate transporter EAAT2's ability to scavenge excess glutamate, regulating

214 the nTS, this study specifically determined EAAT2's role in nTS astrocytes, its influence on neurona

215 amate (excitatory amino acid) transporter 2 (EAAT2; Slc1a2) has been hypothesized to (a) provide isle

216 GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in the

217 ate uptake, a primary function of EAAT2, and EAAT2 small interference RNA completely inhibited ceftri

218 ion of glutamate transporters with either an EAAT2 specific inhibitor or a nonspecific inhibitor of a

219 The EAAT2-specific antagonist dihydrokainate (DHK) was micro

220 sitive to dihydrokainic acid (DHKA), a known EAAT2-specific inhibitor.

221 ized two retinal EAATs from mouse, the GLT-1/EAAT2 splice variant GLT-1c, and EAAT5.

222 ed with low concentration of d-aspartate (an EAAT2 substrate), axon terminals accumulate d-aspartate

223 m exhibited the greatest similarity with the EAAT2 subtype, a transporter believed to be expressed pr

224 rtate (TBOA) but was insensitive to the GLT1/EAAT2 subtype-selective antagonist dihydrokainate and wa

225 tive efficacies (Vmax/K(m)) of the EAAT1 and EAAT2 subtypes for transporting L-cysteine were 10- to 2

226 The kinetic properties of EAAT2, the dominant glutamate transporter in brain astro

227 The gene for EAAT2, the major astrocytic glutamate transporter, gener

228 howed no significant change in the amount of EAAT2, the predominant glial glutamate transporter in th

229 opionic acid analogs as potent inhibitors of EAAT2, the predominant glutamate transporter in forebrai

230 familial form of ALS leads to inhibition of EAAT2 through a mechanism that largely involves activati

231 ateral-preferring EAAT1 and the nonpolarized EAAT2 to the apical surface.

232 rol significantly altered the trafficking of EAAT2 to the plasma membrane as well as their membrane d

233 sistent with the predominant contribution of EAAT2 to this activity.

234 astrocyte line that constantly expressed an EAAT2 transcript containing the 565-nt 5'-UTR and found

235 nsitive and reliable quantitative measure of EAAT2 transcript copy ratios.

236 Ceftriaxone elevated EAAT2 transcription in PHFA through the nuclear factor-k

237 transport, both positive and negative, alter EAAT2 transcription, promoter activity, mRNA, and protei

238 Neuron-stimulated KBBP is required for GLT1/EAAT2 transcriptional activation and is responsible for

239 In the present study, we found that some EAAT2 transcripts contained 5'-untranslated regions (5'-

240 LS is not associated with elevated levels of EAAT2 transcripts retaining intron 7 and skipping exon 9

241 A transgenic mouse approach via crossing EAAT2 transgenic mice with APPSw,Ind.

242 ate uptake was increased about 2-fold in our EAAT2 transgenic mice.

243 e that the use of small molecules to enhance EAAT2 translation may be a therapeutic strategy for the

244 al. characterize a compound that upregulates EAAT2 translation, thereby increasing glutamate uptake b

245 1) activation, which regulates activation of EAAT2 translation.

246 and a pharmacological approach using a novel EAAT2 translational activator, LDN/OSU-0212320, were con

247 t Parawixin1 does not stimulate uptake by an EAAT2 transport mutant (E405D) defective in the potassiu

248 Regulators of EAAT2 transport, both positive and negative, alter EAAT2

249 ctive enhancement of glutamate influx by the EAAT2 transporter subtype through a mechanism that does

250 es that express the GLAST (EAAT1) and GLT-1 (EAAT2) transporter subtypes.

251 aster than previously reported for expressed EAAT2 transporters or the efficiency of these transporte

252 regions of the genes encoding for EAAT1 and EAAT2, two glial EAATs.

253 licing of the dominant glutamate transporter EAAT2 under conditions of neurological stress.

254 regulate astroglial synaptic functions, GLT1/EAAT2, via kappa B-motif binding phosphoprotein (KBBP),

255 EAAT2 was also expressed in neurons in layer I (presumed

256 The specific role of nTS EAAT2 was determined via whole animal and brainstem slic

257 With western blotting, we found that EAAT2 was expressed as a single band until 2 postnatal m

258 e or no internalization of NMO-IgG, AQP4, or EAAT2 was found in primary astrocyte cultures, nor was g

259 tency determined for the inhibition of human EAAT2 was N(4)-[4-(2-bromo-4,5-difluorophenoxy)phenyl]-L

260 in our previous model of glutamate uptake by EAAT2, we predict that the voltage sensitivity of exchan

261 ies of the excitatory amino acid transporter EAAT2 were studied using rapid applications of L-glutama

262 ion of the human glutamate transporter GLT1 (EAAT2), which had been detected in a patient with sporad

263 The glutamate transporter EAAT2, which is primarily localized on astrocytic proces

264 ex was largely confined to the neuropil-like EAAT2, with occasional faint neuronal expression.

265 ytes in both PVL and control cases expressed EAAT2, without qualitative difference in expression.

266 igate whether supplementation of the loss of EAAT2 would delay or rescue the disease progression.