関: EAAT3

WordNet

move something or somebody around; usually over long distances
an exchange of molecules (and their kinetic energy and momentum) across the boundary between adjacent layers of a fluid or across cell membranes
move while supporting, either in a vehicle or in ones hands or on ones body; "You must carry your camping gear"; "carry the suitcases to the car"; "This train is carrying nuclear waste"; "These pipes carry waste water into the river" (同)carry
transport commercially (同)send, ship
street name for lysergic acid diethylamide (同)back breaker, battery-acid, dose, dot, Elvis, loony toons, Lucy in the sky with diamonds, pane, superman, window pane, Zen
any of various water-soluble compounds having a sour taste and capable of turning litmus red and reacting with a base to form a salt
having the characteristics of an acid; "an acid reaction"
a long truck for carrying motor vehicles (同)car transporter
a crane for moving material with dispatch as in loading and unloading ships
pertaining to or containing any of a group of organic compounds of nitrogen derived from ammonia (同)aminic
the radical -NH2 (同)amino_group

PrepTutorEJDIC

(ある場所からある場所へ)…‘を'『輸送する』,運搬する《+名+from+名+to+名》 / 《文》《受動態で》(…で)…‘を'夢中にする,有頂天にする《+名+with+名》 / 〈罪人〉‘を'流刑にする / 〈U〉輸送,運送,輸送(交通)機関(transportation) / 〈C〉(軍隊や軍需品を運ぶ)輸送船,輸送機
酸性の / 酸味のある,すっぱい(sour) / (言葉・態度などが)厳しい,しんらつな / 酸 / すっぱいもの / 《俗》=LSD
自動車運搬用大型トラック

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/24 22:04:10」(JST)

wiki en

Excitatory amino-acid transporters (EAATs), also known as glutamate transporters, belong to the family of neurotransmitter transporters. Glutamate is the principal excitatory neurotransmitter in the vertebrate brain. EAATs serve to terminate the excitatory signal by removal (uptake) of glutamate from the neuronal synapse into neuroglia and neurons.

The EAATs are membrane-bound secondary transporters that superficially resemble ion channels.^[1] These transporters play the important role of regulating concentrations of glutamate in the extracellular space by transporting it along with other ions across cellular membranes.^[2] After glutamate is released as the result of an action potential, glutamate transporters quickly remove it from the extracellular space to keep its levels low, thereby terminating the synaptic transmission.^[1]^[3]

Without the activity of glutamate transporters, glutamate would build up and kill cells in a process called excitotoxicity, in which excessive amounts of glutamate acts as a toxin to neurons by triggering a number of biochemical cascades. The activity of glutamate transporters also allows glutamate to be recycled for repeated release.^[4]

Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues including bone, heart, liver, and testes. They exhibit stereoselectivity for L-glutamate but transport both L- and D-aspartate.

Classes

There are two general classes of glutamate transporters, those that are dependent on an electrochemical gradient of sodium ions (the EAATs) and those that are not (VGLUTs and xCT).^[5] The cystine-glutamate antiporter (xCT) is localised to the plasma membrane of cells whilst vesicular glutamate transporters (VGLUTs) are found in the membrane of glutamate-containing synaptic vesicles. Na⁺-dependent EAATs are also dependent on transmembrane K⁺ and H⁺concentration gradients, and so are also known as 'sodium and potassium coupled glutamate transporters'. Na⁺-dependent transporters have also been called 'high-affinity glutamate transporters', though their glutamate affinity actually varies widely.^[5]

Mitochondria also possess mechanisms for taking up glutamate that are quite distinct from membrane glutamate transporters.^[5]

EAATs

In humans (as well as in rodents), five subtypes have been identified and named EAAT1-5 (SLC1A3, SLC1A2, SLC1A1, SLC1A6, SLC1A7). Subtypes EAAT1-2 are found in membranes of glial cells (astrocytes, microglia, and oligodendrocytes) as well as in endothelial cells, whereas EAAT3-4 is located on neurons.^[6] Finally, EAAT5 is only found in the retina where it is principally localised to photoreceptors and bipolar neurons in the retina.^[7] In rodents, the orthologs for EAAT1-3 are named GLAST, GLT1, and EAAC1, respectively,^[3] whereas the acronyms EAAT4 and EAAT5 are conserved.

When glutamate is taken up into glial cells by the EAATs, it is converted to glutamine and subsequently transported back into the presynaptic neuron, converted back into glutamate, and taken up into synaptic vesicles by action of the VGLUTs.^[3]^[8] This process is named the glutamate-glutamine cycle.

The glial transporters - in particular the various splice variants of GLT-1 (EAAT2) - play the largest role (90%) in regulating extracellular glutamate concentration.^[9]

protein	gene	tissue distribution
EAAT1	SLC1A3	glial and endothelial cells
EAAT2	SLC1A2	glial and endothelial cells
EAAT3	SLC1A1	neurons
EAAT4	SLC1A6	neurons
EAAT5	SLC1A7	retina
VGLUT1	SLC17A7	neurons
VGLUT2	SLC17A6	neurons
VGLUT3	SLC17A8	neurons

VGLUTs

Four types of vesicular glutamate transporters are known, VGLUTs 1–3^[10] (SLC17A7, SLC17A6, and SLC17A8 respectively)^[3] and the novel glutamate/aspartate transporter sialin.^[11] These transporters pack the neurotransmitter into synaptic vesicles so that they can be released into the synapse. VGLUTs are dependent on the proton gradient that exists in the secretory system (vesicles being more acidic than the cytosol). VGLUTs have only between one hundredth and one thousandth the affinity for glutamate that EAATs have.^[3] Also unlike EAATs, they do not appear to transport aspartate.

Pathology

Overactivity of glutamate transporters may result in inadequate synaptic glutamate and may be involved in schizophrenia and other mental illnesses.^[1]

During injury processes such as ischemia and traumatic brain injury, the action of glutamate transporters may fail, leading to toxic buildup of glutamate. In fact, their activity may also actually be reversed due to inadequate amounts of adenosine triphosphate to power ATPase pumps, resulting in the loss of the electrochemical ion gradient. Since the direction of glutamate transport depends on the ion gradient, these transporters release glutamate instead of removing it, which results in neurotoxicity due to overactivation of glutamate receptors.^[12]

Loss of the Na⁺-dependent glutamate transporter EAAT2 is suspected to be associated with neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and ALS–parkinsonism dementia complex.^[13] Also, degeneration of motor neurons in the disease amyotrophic lateral sclerosis has been linked to loss of EAAT2 from patients' brains and spinal cords.^[13]

References

^ ^a ^b ^c Ganel R, Rothstein JD (1999). "Chapter 15, Glutamate transporter dysfunction and neuronal death". In Monyer, Hannah; Gabriel A. Adelmann; Jonas, Peter. Ionotropic glutamate receptors in the CNS. Berlin: Springer. pp. 472–493. ISBN 3-540-66120-4.
^ Zerangue, N, Kavanaugh, MP (1996). "Flux coupling in a neuronal glutamate transporter". Nature 383 (6601): 634–37. doi:10.1038/383634a0. PMID 8857541.
^ ^a ^b ^c ^d ^e Shigeri Y, Seal RP, Shimamoto K (2004). "Molecular pharmacology of glutamate transporters, EAATs and VGLUTs". Brain Res. Brain Res. Rev. 45 (3): 250–65. doi:10.1016/j.brainresrev.2004.04.004. PMID 15210307.
^ Zou JY, Crews FT (2005). "TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition". Brain Res. 1034 (1-2): 11–24. doi:10.1016/j.brainres.2004.11.014. PMID 15713255.
^ ^a ^b ^c Danbolt NC (2001). "Glutamate uptake". Prog. Neurobiol. 65 (1): 1–105. doi:10.1016/S0301-0082(00)00067-8. PMID 11369436.
^ Anderson CM, Swanson RA (2000). "Astrocyte glutamate transport: review of properties, regulation, and physiological functions". Glia 32 (1): 1–14. doi:10.1002/1098-1136(200010)32:1. PMID 10975906.
^ Pow DV, Barnett NL (2000). "Developmental expression of excitatory amino acid transporter 5: a photoreceptor and bipolar cell glutamate transporter in rat retina". Neurosci. Lett. 280 (1): 21–4. doi:10.1016/S0304-3940(99)00988-X. PMID 10696802.
^ Pow DV, Robinson SR (1994). "Glutamate in some retinal neurons is derived solely from glia". Neuroscience 60 (2): 355–66. doi:10.1016/0306-4522(94)90249-6. PMID 7915410.
^ Shachnai L, Shimamoto K, Kanner BI (2005). "Sulfhydryl modification of cysteine mutants of a neuronal glutamate transporter reveals an inverse relationship between sodium dependent conformational changes and the glutamate-gated anion conductance". Neuropharmacology 49 (6): 862–71. doi:10.1016/j.neuropharm.2005.07.005. PMID 16137722.
^ Naito S, Ueda T (January 1983). "Adenosine triphosphate-dependent uptake of glutamate into protein I-associated synaptic vesicles". J. Biol. Chem. 258 (2): 696–9. PMID 6130088.
^ Miyaji T, Echigo N, Hiasa M, Senoh S, Omote H, Moriyama Y (August 2008). "Identification of a vesicular aspartate transporter". Proc. Natl. Acad. Sci. U.S.A. 105 (33): 11720–4. doi:10.1073/pnas.0804015105. PMC 2575331. PMID 18695252. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2575331/.
^ Kim AH, Kerchner GA, Choi DW (2002). "Chapter 1, Blocking Excitotoxicity". In Marcoux, Frank W.. CNS neuroprotection. Berlin: Springer. pp. 3–36. ISBN 3-540-42412-1.
^ ^a ^b Yi JH, Hazell AS (2006). "Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury". Neurochem. Int. 48 (5): 394–403. doi:10.1016/j.neuint.2005.12.001. PMID 16473439.

External links

Glutamate+Transporter at the US National Library of Medicine Medical Subject Headings (MeSH)

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English Journal

Nicotine decreases the activity of glutamate transporter type 3.

Yoon HJ1, Lim YJ2, Zuo Z3, Hur W4, Do SH5.Author information 1Department of Anesthesiology and Pain Medicine, Cheil General Hospital, Kwandong University, Mukjung-dong, Jun-gu, Seoul, South Korea.2Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Yongon-dong, Chongno-gu, Seoul, South Korea.3Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, USA.4Department of Anesthesiology and Pain Medicine, Guro Hospital, Korea University, Guro-dong, Guru-gu, Seoul, South Korea.5Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea. Electronic address: shdo@snu.ac.kr.AbstractNicotine, the main ingredient of tobacco, elicits seizures in animal models and cigarette smoking is regarded as a behavioral risk factor associated with epilepsy or seizures. In the hippocampus, the origin of nicotine-induced seizures, most glutamate uptake could be performed primarily by excitatory amino acid transporter type 3 (EAAT3). An association between temporal lobe epilepsy and EAAT3 downregulation has been reported. Therefore, we hypothesized that nicotine may elicit seizures through the attenuation of EAAT3 activity. We investigated chronic nicotine exposure (72 h) cause reduction of the activity of EAAT3 in a Xenopus oocyte expression system using a two-electrode voltage clamp. The roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) were also determined. Nicotine (0.001-1 μM) resulted in a time- and dose-dependent decrease in EAAT3 activity with maximal inhibition at nicotine concentrations of 0.03 μM or higher and at an exposure time of 72 h. Vmax on the glutamate response was significantly reduced in the nicotine group (0.03 μM for 72 h), but the Km value of EAAT3 for glutamate was not altered. When nicotine-exposed oocytes (0.03 μM for 72 h) were pretreated with phorbol-12-myristate-13-acetate (PMA, a PKC activator), the nicotine-induced reduction in EAAT3 activity was abolished. PKC inhibitors (staurosporine, chelerythrine, and calphostin C) significantly reduced basal EAAT3 activity, but there were no significant differences among the PKC inhibitors, nicotine, and PKC inhibitors+nicotine groups. Similar response patterns were observed among PI3K inhibitors (wortmannin and LY294002), nicotine, and PI3K inhibitors+nicotine. In conclusion, this study suggests that nicotine decreases EAAT3 activity, and that this inhibition seems to be dependent on PKC and PI3K. Our results may provide an additional mechanism for nicotine-induced seizure.
Toxicology letters.Toxicol Lett.2014 Feb 10;225(1):147-52. doi: 10.1016/j.toxlet.2013.12.002. Epub 2013 Dec 16.
Nicotine, the main ingredient of tobacco, elicits seizures in animal models and cigarette smoking is regarded as a behavioral risk factor associated with epilepsy or seizures. In the hippocampus, the origin of nicotine-induced seizures, most glutamate uptake could be performed primarily by excitator
PMID 24355585

Effects of the altered activity of δ-opioid receptor on the expression of glutamate transporter type 3 induced by chronic exposure to morphine.

Wu Q1, Xia S, Lin J, Cao D, Chen W, Liu L, Fu Y, Liang J, Cao M.Author information 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, PR China.AbstractAltered δ-opioid receptor (DOR) activity can affect the activity and function of excitatory amino acid transporter 3 (EAAT3), but the effects of DOR on EAAT3 expression in morphine relapse remain unknown. In this study, a C6δ cell line and SD rats in a conditioned place preference (CPP) reinstatement model were used. Here, we show that EAAT3 protein levels in C6δ cells decreased significantly after chronic exposure to morphine (10 μM) for 48 h and returned to normal 12 h after drug withdrawal. When C6δ cells were re-exposed to 5 μM morphine for 4 h, EAAT3 protein levels again decreased significantly. The selective μ opioid receptor (MOR) specific agonist DAMGO had a similar effect as morphine, and CTOP, a specific MOR blocker, reversed the declined expression of EAAT3 protein triggered by morphine exposure. The selective DOR agonist [d-pen2, 5] enkephalin (DPDPE) significantly increased EAAT3 expression in C6δ cells and even reversed the decreased EAAT3 expression caused by chronic morphine exposure. The non specific antagonist naloxone, but not the DOR inhibitor Naltrindole (NTI), reversed the decreased EAAT3 expression in C6δ cells caused by chronic morphine exposure. In vivo, EAAT3 levels in the prefrontal cortex of rats with morphine-induced CPP reinstatement significantly decreased. Naloxone completely suppressed reinstatement and reversed the decrease in EAAT3 expression induced by morphine re-exposure. In contrast, NTI only weakened CPP reinstatement and exerted no influence on EAAT3 expression. These findings suggest that DOR can affect the expression of EAAT3. However, the morphine-induced down-regulation of EAAT3 in C6δ cells and in the prefrontal cortex of rats may not be mediated by DOR.
Journal of the neurological sciences.J Neurol Sci.2013 Dec 15;335(1-2):174-81. doi: 10.1016/j.jns.2013.09.026. Epub 2013 Sep 25.
Altered δ-opioid receptor (DOR) activity can affect the activity and function of excitatory amino acid transporter 3 (EAAT3), but the effects of DOR on EAAT3 expression in morphine relapse remain unknown. In this study, a C6δ cell line and SD rats in a conditioned place preference (CPP) reinstatem
PMID 24120272

Eriodictyol-7-O- glucoside activates Nrf2 and protects against cerebral ischemic injury.

Jing X1, Ren D2, Wei X1, Shi H1, Zhang X1, Perez RG3, Lou H4, Lou H2.Author information 1Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China.2Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012, China.3Health science center, Paul L. foster School of Medicine, Texas Tech University, El Paso, TX, 79905, USA.4Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China. Electronic address: louhaiyan@sdu.edu.cn.AbstractStroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke.
Toxicology and applied pharmacology.Toxicol Appl Pharmacol.2013 Oct 26. pii: S0041-008X(13)00466-3. doi: 10.1016/j.taap.2013.10.018. [Epub ahead of print]
Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has b
PMID 24512736

Japanese Journal

Three types of neurochemical projection from the bed nucleus of the stria terminalis to the ventral tegmental area in adult mice.

Kudo Takehiro,Uchigashima Motokazu,Miyazaki Taisuke,Konno Kohtarou,Yamasaki Miwako,Yanagawa Yuchio,Minami Masabumi,Watanabe Masahiko
The Journal of neuroscience : the official journal of the Society for Neuroscience 32(50), 18035-18046, 2012-12-12
… In the VTA, VGluT3 was detected in terminals expressing vesicular inhibitory amino acid transporter (VIAAT), plasmalemmal serotonin transporter, or neither. … VGluT2(+) and VGluT3(+) BST neurons further supply additional projections, which may principally convey excitatory or inhibitory inputs, respectively, to the VTA. …
NAID 120005295648

Possible Involvement of Glutamatergic Signaling Machineries in Pathophysiology of Rheumatoid Arthritis

Hinoi Eiichi,Yoneda Yukio
Journal of pharmacological sciences 116(3), 248-256, 2011-07-20
… The prevailing view is that L-glutamate (Glu) functions as an excitatory amino acid neurotransmitter through a number of molecular machineries required for the neurocrine signaling at synapses in the brain. …
NAID 10029894955

脊髄由来ミクログリアの新たな機能制御に関するＡＴＰ受容体の役割

森岡徳光
YAKUGAKU ZASSHI 131(7), 1047-1052, 2011
… Thus, I focused on the ATP-mediated regulation mechanisms for the two important proteins, which are p38 MAP kinase and excitatory amino acid transporters (EAATs), in cultured spinal microglia. …
NAID 130000926993

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★リンクテーブル★

リンク元	「EAAT3」「3型興奮性アミノ酸輸送体」「興奮性アミノ酸トランスポーター3」「SLC1A1」
関連記事	「transport」「excitatory」「transporter」