ライフサイエンスコーパス: EAAT1

1 EAAT1 is a glutamate transporter expressed by astrocytes

2 excitatory amino acid transporter subtype 1 (EAAT1) and its rodent ortholog GLAST are elucidated.

3 hetase, excitatory amino-acid transporter 1 (EAAT1), and EAAT2.

4 opsin, excitatory amino acid transporter 1 (EAAT1), glutamate synthetase (GS), cellular retinaldehyd

5 or for EAAT1, supported by the following: 1) EAAT1 contains two consensus sites for NF-kappaB, 2) mut

6 itatory amino acid transporter subtypes 1-3 (EAAT1-3) resulted in the identification of compound (Z)-

7 the excitatory amino acid transporters 1-3 (EAAT1-3).

8 -specific antisense oligonucleotides against EAAT1.

9 cological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective Glu

10 Labeling with anti-EAAT1, anti-GS, and anti-CRALBP was increased in the Mul

11 g conformer, iChS, transiently accessible as EAAT1 reconfigures from substrate/ion-loaded into a subs

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

13 ted a distinct preference as an inhibitor at EAAT1 (IC50 20 muM) compared to EAAT2 and EAAT3 (IC50 >

14 ogue 4y that displayed an IC50 of 0.8 muM at EAAT1 with a 14- and 9-fold preference over EAAT2 and EA

15 bstantially improved inhibitory potencies at EAAT1 compared to that displayed by the hit, it provided

16 ile differed significantly from that of both EAAT1 and EAAT3 mRNA.

17 Inasmuch as GDNF can increase levels of both EAAT1 and NMDAR1, it may be a useful therapeutic approac

18 reated with GDNF had elevated levels of both EAAT1 and NMDAR1.

19 ransporter subtypes cloned from human brain (EAAT1-3) was examined by measuring transporter-mediated

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

21 function glutamate transporter/anion channel EAAT1, and discovered it caused malformation of astrocyt

22 ytes expressing the human transporter clones EAAT1, EAAT2, or EAAT3, it was found that the pharmacolo

23 as co-repressors of YY1 to further decrease EAAT1 promoter activity, whereas inhibition of HDACs rev

24 d, whereas inhibition of NF-kappaB decreased EAAT1 promoter activity and mRNA/protein levels.

25 Manganese decreased EAAT1 expression via YY1.

26 glutamate transport significantly decreased EAAT1 mRNA levels suggesting that transporter expression

27 utation of NF-kappaB binding sites decreased EAAT1 promoter activity, and 3) activation of NF-kappaB

28 for YY1, 2) overexpression of YY1 decreased EAAT1 promoter activity and mRNA/protein levels, and 3)

29 3 protein, however, we were unable to detect EAAT1 protein.

30 sorder with significant reductions of EAAT4, EAAT1, GluRdelta, IP3R, and NCAM140.

31 Higher expressions of transcripts encoding EAAT1 and EAAT2, but not EAAT3, were detected in the tha

32 th normal and hypertrophied hearts expressed EAAT1 and EAAT3 mRNA.

33 ted specificity of UCPH-101 and UCPH-102 for EAAT1 over EAAT2 and EAAT3 is demonstrated to extend to

34 ters was found to be approximately 1:3:6 for EAAT1, EAAT2, and EAAT3, respectively.

35 cDNA for EAAT1, EAAT2, and EAAT3 was observed, indicating that mR

36 Glu and were not significantly different for EAAT1, EAAT2, or EAAT3, but 2-FAA exhibited higher affin

37 e promoter regions of the genes encoding for EAAT1 and EAAT2, two glial EAATs.

38 is a main positive transcription factor for EAAT1, supported by the following: 1) EAAT1 contains two

39 There was no quantitative change in mRNA for EAAT1, EAAT2, or EAAT3 in ALS motor cortex, even in pati

40 led insight into structural requirements for EAAT1 activity of this scaffold.

41 e astrocyte cultures that express the GLAST (EAAT1) and GLT-1 (EAAT2) transporter subtypes.

42 cloned from animal and human tissue: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5.

43 Two of the three transporters, GLAST (EAAT1) and EAAC1 (EAAT3), are localized to microculture

44 r/excitatory amino acid transporter 1 (GLAST/EAAT1) in EAE cerebellum caused by protein downregulatio

45 y carriers homologous to the mammalian GLAST/EAAT1 transporter.

46 ated EAE modifications through a rapid GLAST/EAAT1 downregulation, whereas incubation of an IL-1 rece

47 nd GABAergic transmissions, along with GLAST/EAAT1 normalization, milder inflammation, and reduced mo

48 Leu-303 or its counterpart Leu-391 in human EAAT1 (hEAAT1) is confirmed by site-directed mutagenesis

49 iques in Xenopus oocytes injected with human EAAT1 cRNA.

50 Residues lining this cavity in EAAT1, including Ser-366, Leu-369, Phe-373, Arg-388, Pro

51 rminus of EAAT3 with the analogous region in EAAT1 eliminated apical localization in MDCK cells.

52 ion conductance in EAATs and suggest that in EAAT1, Arg-388 is a critical element for the structural

53 EGF increased EAAT1 mRNA/protein levels and glutamate uptake via NF-ka

54 in levels, and 3) knockdown of YY1 increased EAAT1 promoter activity and mRNA/protein levels.

55 somer) and 12a (SR-isomer) failed to inhibit EAAT1 uptake (IC(50) values >300 muM).

56 Analogue 9 inhibited EAAT1 in the micromolar range (IC(50) value 20 muM), whe

57 1a (RS-isomer) and 12b (RR-isomer) inhibited EAAT1 (IC(50) values 5.5 and 3.8 muM, respectively), whe

58 th a terminal's secretory face but maximizes EAAT1 between adjacent terminals, thus permitting glutam

59 e, five subtypes have been identified, named EAAT1-5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and E

60 The discovery of this new class of EAAT1-selective inhibitors not only supplements the curr

61 HDACs reversed manganese-induced decrease of EAAT1 expression.

62 ne substituted within a C-terminal domain of EAAT1 abolishes transport in both the forward and revers

63 In addition, by studying the expression of EAAT1 and EAAT2 glutamate transporters, it was possible

64 ined the cellular and temporal expression of EAAT1-3 in the developing human cerebral cortex.

65 results demonstrate that normal function of EAAT1 and EAAT2 is necessary for retinal ganglion cell s

66 via disruption of the ancillary function of EAAT1 as a chloride channel.

67 amined, with IC(50) values for inhibition of EAAT1 and EAAT3 of 5 and 3.8 microM, respectively, corre

68 PH-101 exhibits noncompetitive inhibition of EAAT1, and its binding site in GLAST has been delineated

69 The loss of EAAT1 in glaucoma may account for the elevated level of

70 gical functions, the molecular mechanisms of EAAT1 regulation at the transcriptional level remain to

71 ed against the full-length coding regions of EAAT1, EAAT2, and EAAT3.

72 EGF, whereas YY1 is a negative regulator of EAAT1 with HDACs as co-repressors, mediating the inhibit

73 F-kappaB is a critical positive regulator of EAAT1, mediating the stimulatory effects of EGF, whereas

74 s a role as a critical negative regulator of EAAT1, supported by the following: 1) the EAAT1 promoter

75 101 induces a long-lasting inactive state of EAAT1, whereas the inhibition exerted by closely related

76 performing cell- and region-level studies of EAAT1 and EAAT2 expression in the mediodorsal nucleus of

77 provide evidence that within each subunit of EAAT1, Ala-395 in TM7 resides close to a residue at the

78 ive evaluation of the C-terminal topology of EAAT1 determined by the chemical modification of introdu

79 cysteine pairs in a cysteine-less version of EAAT1 to examine the dynamics of key domains associated

80 ating the inhibitory effects of manganese on EAAT1 regulation.

81 exhibiting 30- and 50-fold selectivity over EAAT1 and EAAT3, respectively.

82 cient to redirect the basolateral-preferring EAAT1 and the nonpolarized EAAT2 to the apical surface.

83 6-associated mutation is a P>R substitution (EAAT1(P>R)) that in transfected cells has a reduced rate

84 e excitatory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3.

85 of EAAT1, supported by the following: 1) the EAAT1 promoter contains multiple consensus sites for YY1

86 Transcripts for both the EAAT1 and EAAT3 transporter subtypes were detected but n

87 Like the EAAT1(P>R) mutation, the chloride-extruding K(+)-Cl(-) c

88 ; the relative efficacies (Vmax/K(m)) of the EAAT1 and EAAT2 subtypes for transporting L-cysteine wer

89 ole of the abnormal anion conductance of the EAAT1(P>R) mutation, and to do this we expressed chlorid

90 oride into cells, rescued the effects of the EAAT1(P>R) mutation.

91 and paralysis, supporting the idea that the EAAT1(P>R) mutation causes abnormal chloride flow from C

92 We expressed this EAAT1(P>R) mutation in glial cells of Drosophila larvae

93 of total EAAT2 and a minor portion of total EAAT1, EAAT3, and EAAT4 were associated with lipid rafts

94 xcitatory amino acid transporter transcripts EAAT1, EAAT2, and EAAT3 was performed in discrete thalam

95 ons of the excitatory amino acid transporter EAAT1 (also known as GLAST), but the underlying pathophy

96 ucleotides against the glutamate transporter EAAT1 decreased the levels of expression of the transpor

97 n do so when the glial glutamate transporter EAAT1 is inhibited.

98 lying transport by the glutamate transporter EAAT1, we mutated each of 24 highly conserved residues (

99 strocytic excitatory amino acid transporter (EAAT1).

100 l framework minimizes glutamate transporter (EAAT1) beneath a terminal's secretory face but maximizes

101 GLAST (for glutamate-aspartate transporter; EAAT1) or EAAC1 (for excitatory amino acid carrier; EAAT