Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease

Zoia, Chiara Paola; Cogliati, Tiziana; Tagliabue, Elena; Cavaletti, Guido; Sala, Gessica; Galimberti, Gloria; Rivolta, Ilaria; Rossi, Vincenzo; Frattola, L.; Ferrarese, Carlo

doi:10.1016/s0197-4580(03)00085-x

Cited by 77 publications

(41 citation statements)

References 51 publications

(64 reference statements)

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“…Amyotrophic lateral sclerosis is a relatively frequent neurodegenerative disease that affects both upper and inferior motoneurons. Reduced glutamate (Glu) transporter, EAAT1, has been described in lateral amyotrophic sclerosis (ALS) tissues in 1995 [14], and recently demonstrated in aging and AD [15]. Looking for the effects of the excitatory aminoacid Glu on neurons, especially on the calcium mediated synthesis of nitric oxide (NO), we found that nitrites and nitrates, as end-products of NO, are measurable in the CSF [16].…”

Section: Introductionmentioning

confidence: 71%

Free Copper, Ferroxidase and SOD1 Activities, Lipid Peroxidation and NO x Content in the CSF. A Different Marker Profile in Four Neurodegenerative Diseases

et al. 2008

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The understanding of oxidative damage in different neurodegenerative diseases could enhance therapeutic strategies. Our objective was to quantify lipoperoxidation and other oxidative products as well as the activity of antioxidant enzymes and cofactors in cerebrospinal fluid (CSF) samples. We recorded data from all new patients with a diagnosis of either one of the four most frequent neurodegenerative diseases: Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and lateral amyotrophic sclerosis (ALS). The sum of nitrites and nitrates as end products of nitric oxide (NO) were increased in the four degenerative diseases and fluorescent lipoperoxidation products in three (excepting ALS). A decreased Cu/Zn-dependent superoxide dismutase (SOD) activity characterized the four diseases. A significantly decreased ferroxidase activity was found in PD, HD and AD, agreeing with findings of iron deposition in these entities, while free copper was found to be increased in CSF and appeared to be a good biomarker of PD.

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Section: Introductionmentioning

confidence: 71%

Free Copper, Ferroxidase and SOD1 Activities, Lipid Peroxidation and NO x Content in the CSF. A Different Marker Profile in Four Neurodegenerative Diseases

et al. 2008

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“…EAAT3 is not only expressed in neurons [28,[51][52][53][54][55][56][57], retinal ganglion cells [58] and glial cells [59,60] but is expressed in a wide variety of nonexcitable cells and non-neuronal tissues including blood platelets [61,62], heart [63], renal podocytes [64], epididymis [65], placenta [66,67] and blood-brain barrier [68].…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Glutamate Transporters by JAK2

Hosseinzadeh

Bhavsar²,

Sopjani³

et al. 2011

Cell Physiol Biochem

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The Janus-activated kinase-2 JAK2 is involved in the signaling of leptin and erythropoietin receptors and mediates neuroprotective effects of the hormones. In theory, JAK2 could be effective through modulation of the glutamate transporters, carriers accounting for the clearance of glutamate released during neurotransmission. The present study thus elucidated the effect of JAK2 on the glutamate transporters EAAT1, EAAT2, EAAT3 and EAAT4. To this end, cRNA encoding the carriers was injected into Xenopus oocytes with or without cRNA encoding JAK2 and glutamate transport was estimated from glutamate induced current (I_glu). I_glu was observed in Xenopus oocytes expressing EAAT1 or EAAT2 or EAAT3 or EAAT4, but not in water injected oocytes. Coexpression of JAK2 resulted in an increase of I_glu by 83% (EAAT1), 67% (EAAT2), 42% (EAAT3) and 126% (EAAT4). As shown for EAAT4 expressing Xenopus oocytes, the effect of JAK2 was mimicked by gain of function mutation ^V617FJAK2 but not by the inactive mutant ^K882EJAK2. Incubation with JAK2 inhibitor AG490 (40 µM) resulted in a gradual decrease of I_glu by 53%, 79% and 92% within 3, 6 and 24 hours. Confocal microscopy and chemiluminescence analysis revealed that JAK2 coexpression increased EAAT4 protein abundance in the cell membrane. Disruption of transcription did not appreciably modify the up-regulation of I_glu in EAAT4 expressing oocytes. The decay of I_glu following inhibition of carrier insertion with brefeldin A was similar in oocytes expressing EAAT4 + JAK2 and oocytes expressing EAAT4 alone, indicating that JAK2 did not appreciably affect carrier retrieval from the membrane. In conclusion, JAK2 is a novel powerful regulator of glutamate transporters and thus participates in the protection against excitotoxicity.

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“…Results are relevant to the understanding of the mechanisms of excitotoxicity involved in neuronal damage associated with ischemia and some neurodegenerative diseases. While acute transport-mediated glutamate release and energy depletion are associated with ischemia and hypoglycemia [9,52] chronic failure of glutamate uptake might be associated with Huntington's and Alzheimer's diseases [15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, decreased glutamate uptake and expression of glutamate transporters has been associated with Alzheimer's and Huntington's diseases, and excitotoxicity has been suggested as a component of the process of neurodegeneration linked to these pathologies [15][16][17][18][19]. Studies have shown that decreased expression of glutamate transporters in vivo, promotes the extracellular accumulation of glutamate and neuronal death [20,21].…”

Section: Introductionmentioning

confidence: 99%

Cerebellar Granule Neurons are More Vulnerable to Transient Transport-Mediated Glutamate Release than to Glutamate Uptake Blockade. Correlation with Excitatory Amino Acids Levels

et al. 2007

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The extracellular concentration of glutamate is highly regulated due to its excitotoxic nature. Failure of glutamate uptake or reversed activation of its transporters contributes to neurodegeneration related to some pathological conditions. We have compared the neurotoxicity of the substrate glutamate uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), which promotes glutamate release by hetero-exchange, with that of DL-threo-beta-benzyloxyaspartate (DL-TBOA), a non-substrate inhibitor, in cerebellar granule cell cultures. PDC substantially increases the extracellular concentration of glutamate during 30 min exposure and causes neuronal death at high concentrations, while DL-TBOA neurotoxicity is only observed after long-term exposure (8-24 h). During mitochondrial inhibition by 3-nitropropionic acid (3-NP), PDC-induced neuronal death is facilitated, but not that of DL-TBOA. In cultures containing a higher population of astrocytes DL-TBOA-induced increase in glutamate levels is more pronounced, but neuronal death is only triggered in the presence of 3-NP. Results suggest that cerebellar granule neurons are more vulnerable to acute transport-mediated glutamate release than to uptake blockade, which correlates with the extracellular excitatory amino acids levels.

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Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease

Cited by 77 publications

References 51 publications

Free Copper, Ferroxidase and SOD1 Activities, Lipid Peroxidation and NO x Content in the CSF. A Different Marker Profile in Four Neurodegenerative Diseases

Free Copper, Ferroxidase and SOD1 Activities, Lipid Peroxidation and NO x Content in the CSF. A Different Marker Profile in Four Neurodegenerative Diseases

Regulation of the Glutamate Transporters by JAK2

Cerebellar Granule Neurons are More Vulnerable to Transient Transport-Mediated Glutamate Release than to Glutamate Uptake Blockade. Correlation with Excitatory Amino Acids Levels

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