HUGO ID Detailed Result 10940


HUGO ID 10940
Symbol SLC1A2
Name solute carrier family 1 (glial high affinity glutamate transporter), member 2
#Occurrence 129
#Paper 9

 


PMID Match String Actual String Score Flanking text Edited by Edit
9745361GLT1GLT12.3in the structures of at least three transporter subtypes (GLT1, GLT1 GLAST and EAAC1 and shown to regulate transport rate via 
9745361GLT1GLT12.3amino acid carriers have now been identified GLAST (EAAT1), EAAT1 GLT1 (EAAT2), EAAT2 EAAC1 (EAAT3), EAAT3 EAAT4 and EAAT5 (Refs Refs 
9745361EAAT2EAAT21.5carriers have now been identified GLAST (EAAT1), EAAT1 GLT1 (EAAT2), EAAT2 EAAC1 (EAAT3), EAAT3 EAAT4 and EAAT5 (Refs Refs 1 2 
9745361GLT1GLT12.3In studies to localize the isoforms GLT1 and GLAST appear to be restricted to brain astrocytes 11 
9745361GLT1GLT12.3GLT1 is the most abundant glutamate transporter and represents about 1% 
9745361GLT1GLT12.3In astrocytic membranes GLT1 and GLAST localize preferentially to the parts of the plasma 
9745361GLT1GLT12.3Moreover the expression of GLT1 and GLAST is under the control of neuronal soluble factors 
9745361GLT1GLT12.3tissue damage resulted from loss of the glial transporters particularly GLT1 (Ref Ref 25 
9745361GLT1GLT12.3Indeed knockout mice lacking GLT1 undergo lethal spontaneous seizures increased susceptibility to acute brain injury 
9745361GLT1GLT12.3Indeed the transport activities of GLT1 EAAC1 and GLAST are equally inhibited by oxidants via a 
9745361GLT1GLT12.3EAAC1 GLT1 and GLAST exhibit redox-sensing properties 
9745361GLT1GLT12.3EAAC1 GLAST GLT1 EAAT4 and EAAT5 carry different cysteine residues in their sequences 
9745361GLT1GLT12.3glutamate uptake activity apparently owing to a selective loss of GLT1 in the spinal cord and motor cortex of patients with 
9745361GLT1GLT12.3The mechanism(s) mechanism s leading to loss of GLT1 are not fully understood 
9745361GLT1GLT12.3The steady-state level of GLT1 mRNA was apparently unchanged leading investigators initially to suspect a 
9745361GLT1GLT12.3or the internalization and/or and or degradation of post-translationally damaged GLT1 (Ref Ref 51 
9745361GLT1GLT12.3and/or and or producing a dominant negative effect on normal GLT1 (Ref Ref 52 
9745361GLT1GLT12.3tyrosine nitration of glutamate transporters 43 and marked loss of GLT1 in the spinal cord 58 
9745361GLT1GLT12.3shown to form adducts with a number of proteins including GLT1 by reaction at sulphydryls or other vulnerable groups 66 
9745361GLT1GLT12.3As the glutamate transporters GLT1 in particular are crucial in maintaining glutamate homeostasis 6 32 
12614931EAAT2EAAT21.5receptor subunit and a much greater perisomatic expression of the EAAT2 protein the glial glutamate transporter which is particularly vulnerable to 
12684448GLT-1GLT-12.5and GFAP 1 400 (Dako, Dako Glostrup Denmark glutamate transporter GLT-1 (also also known as EAAT2 0.17 microg/ml microg ml (kindly 
12684448EAAT2EAAT22.5Dako Glostrup Denmark glutamate transporter GLT-1 (also also known as EAAT2 0.17 microg/ml microg ml (kindly kindly supplied by Jeff Rothstein 
12684448GLT-1GLT-12.5an explanation for previous reports of oxidative modifications of the GLT-1 transporter in ALS (Pedersen Pedersen et al. 1998 Trotti et 
12893007EAAT2EAAT21.8There is specific loss of the glial glutamate transporter protein EAAT2 in spinal cord of sALS cases ([ Fray et al 
12893007EAAT2EAAT21.8of HNE was cause of modification of astrocytic glutamate transporter EAAT2 and impaired glutamate transport in ALS ( Pedersen et al 
14690536GLT-1GLT-12.5SOD1 in primary cultures of astrocytes down-regulates the glutamate transporter GLT-1 lack of involvement of oxidative stress 
14690536GLT-1GLT-12.5astrocytes produced down-regulation of the levels of a glutamate transporter GLT-1 without alterations in its mRNA level hSOD1(G93A) hSOD1 G93A or 
14690536GLT-1GLT-12.5hSOD1wt expression caused a decrease of the monomeric form of GLT-1 without increasing oxidative multimers of GLT-1 
14690536GLT-1GLT-12.5the monomeric form of GLT-1 without increasing oxidative multimers of GLT-1 
14690536GLT-1GLT-12.5The effects were selective to GLT-1 since another glutamate transporter GLAST protein and mRNA levels were 
14690536GLT-1GLT-12.5Reflecting the decrease in GLT-1 protein 3H d-aspartate uptake was reduced in cultures expressing hSOD1(G93A) 
14690536GLT-1GLT-12.5The hSOD1-induced decline in GLT-1 protein and 3H d-aspartate uptake was not blocked by the 
14690536GLT-1GLT-12.5This study suggests that levels of GLT-1 protein in astrocytes are reduced rapidly by overexpression of hSOD1 
14698606GLT-1GLT-11.0Specifically the astrocytic glutamate transporter GLT-1 (also also known as the excitatory amino acid transporter EAAT-2 
14698606EAAT2EAAT-21.0GLT-1 (also also known as the excitatory amino acid transporter EAAT-2 appears to be particularly affected 34 and 35 
14698606GLT-1GLT-11.0Indeed the GLT-1 transporter which is damaged in ALS is concentrated in astrocytic 
15031734GLT-1GLT-11.0inhibition of the neuronal glucose transporter type-3 the glutamate transporter GLT-1 (Ref Ref 13 as well as the Na K ATPases 
16026864EAAT2EAAT21.0can be caused by oxidative damage to the glutamate transporter EAAT2 or by aberrant RNA processing 22 
17719032GLT-1GLT-11.0In wild-type animals immunoreactivity for the astrocytic glutamate transporter GLT-1 was particularly strong around ventral horn MNs 
17719032GLT-1GLT-11.0However a marked loss of ventral horn GLT-1 was observed along with substantial MN damage prior to onset 
17719032GLT-1GLT-11.0markedly diminished the loss of both MNs and of astrocytic GLT-1 labeling 
17719032GLT-1GLT-11.0resulting from a selective loss of the astrocytic glutamate transporter GLT-1 suggested an excitotoxic contribution ( Rothstein et al. 1992 and 
17719032GLT-1GLT-11.0loss in these animals but also slows the loss of GLT-1 glutamate transporter in ventral horn regions near MNs consistent with 
17719032GLT-1GLT-11.01 8000 ip 1 2000 if Sternberger Monoclonals Berkeley CA GLT-1 1 1000 Chemicon Temecula CA 3-nitrotyrosine 10_amp_#xa0;_amp_#x3bc;g/ml, 10_amp_#xa0 _amp_#x3bc g 
17719032GLT-1GLT-11.0For examination of NT and GLT-1 labeling staining in the neuropil surrounding ventral horn MNs care 
17719032GLT-1GLT-11.0For GLT-1 fluorescence was measured in 5-_amp_#x3bc m zones surrounding the MNs 
17719032GLT-1GLT-11.0from the center of a neuron a region lacking specific GLT-1 labeling was subtracted prior to normalization of values to WT 
17719032GLT-1GLT-11.0were from the following sources SMI-32 Sternberger Monoclonals Berkeley CA GLT-1 Chemicon Temecula CA 3-nitrotyrosine Upstate Biotechnology Waltham MA 
17719032GLT-1GLT-11.0Tu et al. 1996 and a specific decrease of the GLT-1 glutamate transporter has been reported in ventral horn of the 
17719032GLT-1GLT-11.0Finally there was a marked and consistent decrease in GLT-1 staining most prominent in ventral horn 
17719032GLT-1GLT-11.0Notably in wild-type animals GLT-1 labeling often showed a rim of particularly strong labeling immediately 
17719032GLT-1GLT-11.0Quantification of GLT-1 labeling in the neuropil surrounding MNs revealed a sharp decrease 
17719032GLT-1GLT-11.0in the neuropil surrounding MNs revealed a sharp decrease in GLT-1 labeling surrounding MNs in sham-treated transgenic animals (Tg-S) Tg-S 
17719032GLT-1GLT-11.0NAS on NT labeling NAS completely prevented the loss of GLT-1 labeling ( Fig 4 
17719032GLT-1GLT-11.0Howland et al. 2002 we observe substantial loss of the GLT-1 glutamate transporter most evident in the ventral horn in close 
17719032GLT-1GLT-11.0preservation not only of ventral horn MNs but also of GLT-1 labeling near ventral horn MNs 
17719032GLT-1GLT-11.0protection by NAS of MNs themselves as well as of GLT-1 levels in the adjacent astrocytes is most consistent with the 
17719032GLT-1GLT-11.0Indeed observations that substantial loss of GLT-1 preceded much of the MN loss ( Howland et al. 
17719032GLT-1GLT-11.0red A 3-nitrotyrosine (B), B or the astrocytic glutamate transporter GLT-1 (green) green along with SMI-32 (red, red C 
17719032GLT-1GLT-11.0Finally note the rim of strong GLT-1 labeling surrounding MNs in wild-type animals and the distinct loss 
17719032GLT-1GLT-11.0Fig 4._amp_#xa0 Loss of GLT-1 in ventral horn astrocytes of G93A rats and preservation by 
17719032GLT-1GLT-11.0(A) A GLT-1 immunofluorescence photomicrographs show the ventral horn region of lumbar spinal 
17719032GLT-1GLT-11.0(upon upon termination of the 30-day intrathecal infusions stained for GLT-1 (40, 40 400_amp_#xd7 and for SMI-32 (right, right 400_amp_#xd7 
17719032GLT-1GLT-11.0Note the strong GLT-1 labeling surrounding MNs and throughout ventral horn MN clusters in 
17719032GLT-1GLT-11.0show clusters of ventral horn motor neurons with strong astrocytic GLT-1 labeling arrowhead shows persistent strong GLT-1 labeling in dorsal horn 
17719032GLT-1GLT-11.0neurons with strong astrocytic GLT-1 labeling arrowhead shows persistent strong GLT-1 labeling in dorsal horn of untreated transgenic animals 
17719032GLT-1GLT-11.0(B) B Quantification of labeling graph shown quantification of GLT-1 labeling in 5-_amp_#x3bc m zones surrounding each MN (compiled compiled 
9745361glt 1glt11.0specific _amp_#x2018;redox sensing' elements consisting of cysteine residues have been identified in the structures of at least three transporter subtypes glt1 glast and eaac1 and shown to regulate transport rate via thiol disulphide redox interconversion.  
9745361glt 1glt11.0five different isoforms of glutamate transporters or excitatory amino acid carriers have now been identified: glast eaat1 glt1 eaat2 eaac1 eaat3 eaat4 and eaat5 refs [ 1 2 3 4 5 ] .  
9745361glt 1glt11.0in studies to localize the isoforms glt1 and glast appear to be restricted to brain astrocytes [ 11 12 ] and are expressed in different proportions in different regions.  
9745361glt 1glt11.0glt1 is the most abundant glutamate transporter and represents about 1% of the total brain membrane protein[ 6 13 ] with highest concentrations in the hippocampus and cerebral cortex.  
9745361glt 1glt11.0in astrocytic membranes glt1 and glast localize preferentially to the parts of the plasma membrane that face neuropil with lower levels in the parts facing pia mater capillary endothelium other astrocytes and neuronal cell bodie 
9745361glt 1glt11.0moreover the expression of glt1 and glast is under the control of neuronal soluble factors including glutamate itself [ 14 ].  
9745361glt 1glt11.0the most dramatic elevation of extracellular glutamate levels and tissue damage resulted from loss of the glial transporters particularly glt1 ref [ 25 ] .  
9745361glt 1glt11.0indeed knockout mice lacking glt1 undergo lethal spontaneous seizures increased susceptibility to acute brain injury and die prematurely with virtually no survivors three months after birth [ 26 ].  
9745361glt 1glt11.0indeed the transport activities of glt1 eaac1 and glast are equally inhibited by oxidants via a direct action on the transporter proteins.  
9745361glt 1glt11.0eaac1 glt1 and glast exhibit redox sensing properties.  
9745361glt 1glt11.0eaac1 glast glt1 eaat4 and eaat5 carry different cysteine residues in their sequences ranging from a minimum of two for eaat4 to a maximum of 11 for eaat5 ref [ 5 ] .  
9745361glt 1glt11.0sporter defect and neurodegeneration has been demonstrated by rothstein and collegues [ 50 ]: they have reported a remarkable loss of glutamate uptake activity apparently owing to a selective loss of glt1 in the spinal cord and motor cortex of patients with the disease.  
9745361glt 1glt11.0the mechanism s leading to loss of glt1 are not fully understood.  
9745361glt 1glt11.0the steady state level of glt1 mrna was apparently unchanged leading investigators initially to suspect a block of translation or the internalization and/or degradation of post translationally damaged glt1 ref [ 51 ] .  
9745361glt 1glt11.0 mrna was apparently unchanged leading investigators initially to suspect a block of translation or the internalization and/or degradation of post translationally damaged glt1 ref [ 51 ] .  
9745361glt 1glt11.0 of abnormal glt1mrnas including intron retention and exon skipping whose processing could lead to unstable proteins undergoing rapid degradation and/or producing a dominant negative effect on normal glt1 ref [ 52 ] .  
9745361glt 1glt11.0s of sod1 may result in defective glutamate transport since transgenic mice expressing an als linked sod1 mutation show increased tyrosine nitration of glutamate transporters[ 43 ] and marked loss of glt1 in the spinal cord [ 58 ].  
9745361glt 1glt11.0ion of 4 hydroxynonenal an aldehydic product of lipid peroxidative processes which by itself mimicked uptake inhibition. 4 hydroxynomenal was shown to form adducts with a number of proteins including glt1 by reaction at sulphydryls or other vulnerable groups [ 66 ].  
9745361glt 1glt11.0as the glutamate transporters glt1 in particular are crucial in maintaining glutamate homeostasis[ 6 32 33 ] eventual oxidative damage of the transporters in vivo is predicted to have major neurotoxic consequences.  
12684448glt 1glt 11.0cultures were fixed in 4% paraformaldehyde blocked and exposed to primary antibody [smi 32 1:5000 and gfap 1:400 dako glostrup denmark ; glutamate transporter glt 1 also known as eaat2 0.17 microg/ml kindly supplied by jeff rothstein johns hopkins university baltimore md ; 3 nitrotyrosine 10 microg/ml upstate biotechnology waltham ma ].  
12684448glt 1glt 11.0in addition the suggestion that the ros can exit mns and affect surrounding astrocytes provides an explanation for previous reports of oxidative modifications of the glt 1 transporter in als pedersen et al. 1998 ; trotti et al. 1999 ; deitch et al. 2002 .  
12684448glt 1glt 11.0c under confocal microscopy the close spatial relationship between the mn smi 32 red and glial glutamate transporters anti glt 1 green is apparent.  
14690536glt 1glt 11.0expression of sod1 g93a or wild type sod1 in primary cultures of astrocytes down regulates the glutamate transporter glt 1: lack of involvement of oxidative stress.  
14690536glt 1glt 11.0using western blotting immunocytochemistry and rt pcr it was shown that expression of either hsod1 g93a or hsod1wt in astrocytes produced down regulation of the levels of a glutamate transporter glt 1 without alterations in its mrna level. hsod1 g93a or hsod1wt expression caused a decrease of the monomeric form of glt 1 without increasing oxidative multimers of glt 1.  
14690536glt 1glt 11.0 without alterations in its mrna level. hsod1 g93a or hsod1wt expression caused a decrease of the monomeric form of glt 1 without increasing oxidative multimers of glt 1.  
14690536glt 1glt 11.0the effects were selective to glt 1 since another glutamate transporter glast protein and mrna levels were not altered.  
14690536glt 1glt 11.0reflecting the decrease in glt 1 protein [3h]d aspartate uptake was reduced in cultures expressing hsod1 g93a or hsod1wt.  
14690536glt 1glt 11.0the hsod1 induced decline in glt 1 protein and [3h]d aspartate uptake was not blocked by the antioxidant trolox nor potentiated by antioxidant depletion using catalase and glutathione peroxidase inhibitors.  
14690536glt 1glt 11.0this study suggests that levels of glt 1 protein in astrocytes are reduced rapidly by overexpression of hsod1 and is due to a property shared between the wild type and g93a mutant form but does not involve the production of intracellular ox 
14690536excitatory amino acid transporter 2excitatory amino acid transporter 21.0excitatory amino acid transporter 2|sod1 g93a protein|superoxide dismutase 1|superoxide dismutase|  
14698606glt 1glt 11.0specifically the astrocytic glutamate transporter glt 1 also known as the excitatory amino acid transporter eaat 2 appears to be particularly affected [ 34 and 35 ].  
14698606glt 1glt 11.0indeed the glt 1 transporter which is damaged in als is concentrated in astrocytic processes directly abutting motor neurons [ 55 ].  
15031734glt 1glt 11.0 glutamate and glucose from cell culture 12 whereas hne modifies proteins resulting in a multitude of effects including inhibition of the neuronal glucose transporter type 3 the glutamate transporter glt 1 ref 13 as well as the na + +k + atpases 14 .  
17719032glt 1glt 11.0in wild type animals immunoreactivity for the astrocytic glutamate transporter glt 1 was particularly strong around ventral horn mns.  
17719032glt 1glt 11.0however a marked loss of ventral horn glt 1 was observed along with substantial mn damage prior to onset of symptoms 90_amp_#x2013;100_amp_#xa0;days in the g93a rats.  
17719032glt 1glt 11.0compared to sham treated g93a animals 30 day nas infusions starting at 67 _amp_#xb1; 2_amp_#xa0;days of age markedly diminished the loss of both mns and of astrocytic glt 1 labeling.  
17719032glt 1glt 11.0although the cause of most cases is unknown observations of deficiencies in glutamate uptake resulting from a selective loss of the astrocytic glutamate transporter glt 1 suggested an excitotoxic contribution [rothstein et al. 1992] and [rothstein et al. 1995] .  
17719032glt 1glt 11.0we find that this treatment slows not only mn loss in these animals but also slows the loss of glt 1 glutamate transporter in ventral horn regions near mns consistent with the idea that ca ampa channel activation on mns contributes to the loss of astrocytic glutamate transport.  
17719032glt 1glt 11.0 stains were carried out on floating sections blocked 10% fbs 1_amp_#xa0;h and exposed to primary antibody in 10% fbs 0.3% triton x 100 smi 32 1:8000 ip 1:2000 if sternberger monoclonals berkeley ca; glt 1 1:1000 chemicon temecula ca; 3 nitrotyrosine 10_amp_#xa0;_amp_#x3bc;g/ml upstate biotechnology waltham ma .  
17719032glt 1glt 11.0for examination of nt and glt 1 labeling staining in the neuropil surrounding ventral horn mns care was taken to ensure that all slices from each experiment were labeled using identical primary and secondary antibody exposures and  
17719032glt 1glt 11.0for glt 1 fluorescence was measured in 5 _amp_#x3bc;m zones surrounding the mns.  
17719032glt 1glt 11.0for this measure non specific background fluorescence from the center of a neuron a region lacking specific glt 1 labeling was subtracted prior to normalization of values to wt as above.  
17719032glt 1glt 11.0antibodies were from the following sources: smi 32 sternberger monoclonals berkeley ca; glt 1 chemicon temecula ca; 3 nitrotyrosine upstate biotechnology waltham ma.  
17719032glt 1glt 11.0itrotyrosine labeling and loss of astrocytic glutamate transport in sod1 mutant rodent models of als [alexander et al. 2000] [ferrante et al. 1997] and [tu et al. 1996] and a specific decrease of the glt 1 glutamate transporter has been reported in ventral horn of the g93a rats that are the subject of this study howland et al. 2002 .  
17719032glt 1glt 11.0finally there was a marked and consistent decrease in glt 1 staining most prominent in ventral horn.  
17719032glt 1glt 11.0notably in wild type animals glt 1 labeling often showed a rim of particularly strong labeling immediately surrounding mn somata whereas even in the presymptomatic animals this rim was often conspicuously absent fig 2 c .  
17719032glt 1glt 11.0quantification of glt 1 labeling in the neuropil surrounding mns revealed a sharp decrease in glt 1 labeling surrounding mns in sham treated transgenic animals tg s .  
17719032glt 1glt 11.0however in contrast to the paucity of effect of nas on nt labeling nas completely prevented the loss of glt 1 labeling fig 4 .  
17719032glt 1glt 11.0in agreement with prior studies of these animals howland et al. 2002 we observe substantial loss of the glt 1 glutamate transporter most evident in the ventral horn in close proximity to mns in late presymptomatic animals 97_amp_#xa0;days shortly before an acceleration in the rate of mn death with developmen 
17719032glt 1glt 11.0the primary new findings of present studies are that animals treated with the ca ampa channel blocker nas demonstrate a marked preservation not only of ventral horn mns but also of glt 1 labeling near ventral horn mns.  
17719032glt 1glt 11.0s generators in response to ca ampa channel activation taken together with present observations of strong oxidative damage in the vicinity of mns and protection by nas of mns themselves as well as of glt 1 levels in the adjacent astrocytes is most consistent with the primary relevant effect of nas being mn ca ampa channel blockade.  
17719032glt 1glt 11.0indeed observations that substantial loss of glt 1 preceded much of the mn loss howland et al. 2002 and that increasing the level of this transporter slows disease onset guo et al. 2003 whereas decreasing its levels accelerates disease in g93a transg 
17719032glt 1glt 11.0d from 97 _amp_#xb1; 2 day old wild type and g93a transgenic rats and stained for glial fibrillary acidic protein gfap green and smi 32 red a 3 nitrotyrosine b or the astrocytic glutamate transporter glt 1 green along with smi 32 red c .  
17719032glt 1glt 11.0finally note the rim of strong glt 1 labeling surrounding mns in wild type animals and the distinct loss of labeling surrounding mns in the transgenics.  
17719032glt 1glt 11.0fig. 4._amp_#xa0;loss of glt 1 in ventral horn astrocytes of g93a rats and preservation by nas.  
17719032glt 1glt 11.0 a glt 1 immunofluorescence: photomicrographs show the ventral horn region of lumbar spinal cord sections derived from 97 _amp_#xb1; 2 day old rats upon termination of the 30 day intrathecal infusions stained 
17719032glt 1glt 11.0nofluorescence: photomicrographs show the ventral horn region of lumbar spinal cord sections derived from 97 _amp_#xb1; 2 day old rats upon termination of the 30 day intrathecal infusions stained for glt 1 40 400_amp_#xd7; and for smi 32 right 400_amp_#xd7; .  
17719032glt 1glt 11.0note the strong glt 1 labeling surrounding mns and throughout ventral horn mn clusters in wild type wt animals in contrast to the preferential loss of ventral horn labeling with preservation of dorsal horn labeling in tra 
17719032glt 1glt 11.0arrows show clusters of ventral horn motor neurons with strong astrocytic glt 1 labeling; arrowhead shows persistent strong glt 1 labeling in dorsal horn of untreated transgenic animals.  
17719032glt 1glt 11.0 b quantification of labeling: graph shown quantification of glt 1 labeling in 5 _amp_#x3bc;m zones surrounding each mn compiled from 4 independent experiments _amp_#x3e; 100 surround regions for wt tg s and tg nas conditions; 3 animals _amp_#x3e; 60 regions for tg  
17719032excitatory amino acid transporter 2excitatory amino acid transporter 21.0excitatory amino acid antagonists|excitatory amino acid transporter 2|glial fibrillary acidic protein|1 naphthylacetylspermine|spermine|sod1 g93a protein|superoxide dismutase|