Activation of catechol‐O‐methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons
Identifieur interne : 002A87 ( Main/Exploration ); précédent : 002A86; suivant : 002A88Activation of catechol‐O‐methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons
Auteurs : Guowei Huang [Canada, République populaire de Chine] ; Magdalena Dragan [Canada] ; David Freeman [Canada] ; John X. Wilson [Canada, États-Unis]Source :
- Glia [ 0894-1491 ] ; 2005-07.
English descriptors
- KwdEn :
- Amino Acids (metabolism), Animals, Astrocytes (enzymology), Catechol O-Methyltransferase (metabolism), Cells, Cultured, Chromatography, High Pressure Liquid, Enzyme Activation (physiology), Homocysteine (biosynthesis), Homocysteine (metabolism), Hydroxybenzoates (metabolism), Neurons (metabolism), Rats, Rats, Wistar, Sulfhydryl Compounds (metabolism), brain, dihydroxybenzoic acid, dopamine, entacapone, levodopa.
- MESH :
- chemical , biosynthesis : Homocysteine.
- chemical , metabolism : Amino Acids, Catechol O-Methyltransferase, Homocysteine, Hydroxybenzoates, Sulfhydryl Compounds.
- enzymology : Astrocytes.
- metabolism : Neurons.
- physiology : Enzyme Activation.
- Animals, Cells, Cultured, Chromatography, High Pressure Liquid, Rats, Rats, Wistar.
Abstract
Elevation of the total homocysteine (tHcy) concentration in plasma has been implicated in neurodegeneration in patients with stroke, dementia, Alzheimer disease, and Parkinson disease. Because the mechanisms controlling brain tHcy are unknown, the present study investigated its synthesis and transport in primary rat brain cell cultures. We found that the catechol‐O‐methyltransferase (COMT) substrate 3,4‐dihydroxybenzoic acid (DHB) increased export of tHcy in astrocytes, but not in neurons. The export mechanism was selective for tHcy over cyst(e)ine, total glutathione (tGSH) or cysteinylglycine (Cys‐Gly). tHcy export from astrocytes was also induced by the COMT substrates levodopa (L‐DOPA), dopamine and quercetin, and it was blocked by the COMT inhibitors tropolone and entacapone. This export was associated with increased synthesis of tHcy because both intracellular and extracellular tHcy concentrations rose during COMT activation. Incubation in cyst(e)ine‐deficient medium inhibited the tHcy export response to COMT activation. Exogenous tHcy (100 μM) was accumulated into neurons, but not into astrocytes. We conclude that activation of COMT causes sustained synthesis of Hcy in astrocytes and transport of this amino acid to neurons.© 2005 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/glia.20185
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000983
- to stream Istex, to step Curation: 000983
- to stream Istex, to step Checkpoint: 000D15
- to stream PubMed, to step Corpus: 001253
- to stream PubMed, to step Curation: 001253
- to stream PubMed, to step Checkpoint: 001253
- to stream Ncbi, to step Merge: 000518
- to stream Ncbi, to step Curation: 000518
- to stream Ncbi, to step Checkpoint: 000518
- to stream Main, to step Merge: 002E19
- to stream Main, to step Curation: 002A87
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Activation of catechol‐O‐methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons</title><author><name sortKey="Huang, Guowei" sort="Huang, Guowei" uniqKey="Huang G" first="Guowei" last="Huang">Guowei Huang</name></author><author><name sortKey="Dragan, Magdalena" sort="Dragan, Magdalena" uniqKey="Dragan M" first="Magdalena" last="Dragan">Magdalena Dragan</name></author><author><name sortKey="Freeman, David" sort="Freeman, David" uniqKey="Freeman D" first="David" last="Freeman">David Freeman</name></author><author><name sortKey="Wilson, John X" sort="Wilson, John X" uniqKey="Wilson J" first="John X." last="Wilson">John X. Wilson</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:5E2166F0CF3B4D3560BB1C2549EB924AF069A302</idno><date when="2005" year="2005">2005</date><idno type="doi">10.1002/glia.20185</idno><idno type="url">https://api-v5.istex.fr/document/5E2166F0CF3B4D3560BB1C2549EB924AF069A302/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000983</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000983</idno><idno type="wicri:Area/Istex/Curation">000983</idno><idno type="wicri:Area/Istex/Checkpoint">000D15</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000D15</idno><idno type="wicri:doubleKey">0894-1491:2005:Huang G:activation:of:catechol</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:15779086</idno><idno type="wicri:Area/PubMed/Corpus">001253</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001253</idno><idno type="wicri:Area/PubMed/Curation">001253</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001253</idno><idno type="wicri:Area/PubMed/Checkpoint">001253</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001253</idno><idno type="wicri:Area/Ncbi/Merge">000518</idno><idno type="wicri:Area/Ncbi/Curation">000518</idno><idno type="wicri:Area/Ncbi/Checkpoint">000518</idno><idno type="wicri:doubleKey">0894-1491:2005:Huang G:activation:of:catechol</idno><idno type="wicri:Area/Main/Merge">002E19</idno><idno type="wicri:Area/Main/Curation">002A87</idno><idno type="wicri:Area/Main/Exploration">002A87</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Activation of catechol‐O‐methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons</title><author><name sortKey="Huang, Guowei" sort="Huang, Guowei" uniqKey="Huang G" first="Guowei" last="Huang">Guowei Huang</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nutrition Research Unit, School of Public Health, Tianjin Medical University, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Dragan, Magdalena" sort="Dragan, Magdalena" uniqKey="Dragan M" first="Magdalena" last="Dragan">Magdalena Dragan</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Freeman, David" sort="Freeman, David" uniqKey="Freeman D" first="David" last="Freeman">David Freeman</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, University of Western Ontario, London, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Wilson, John X" sort="Wilson, John X" uniqKey="Wilson J" first="John X." last="Wilson">John X. Wilson</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Kimball Tower 410, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Glia</title><title level="j" type="abbrev">Glia</title><idno type="ISSN">0894-1491</idno><idno type="eISSN">1098-1136</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2005-07">2005-07</date><biblScope unit="volume">51</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="47">47</biblScope><biblScope unit="page" to="55">55</biblScope></imprint><idno type="ISSN">0894-1491</idno></series><idno type="istex">5E2166F0CF3B4D3560BB1C2549EB924AF069A302</idno><idno type="DOI">10.1002/glia.20185</idno><idno type="ArticleID">GLIA20185</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0894-1491</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acids (metabolism)</term><term>Animals</term><term>Astrocytes (enzymology)</term><term>Catechol O-Methyltransferase (metabolism)</term><term>Cells, Cultured</term><term>Chromatography, High Pressure Liquid</term><term>Enzyme Activation (physiology)</term><term>Homocysteine (biosynthesis)</term><term>Homocysteine (metabolism)</term><term>Hydroxybenzoates (metabolism)</term><term>Neurons (metabolism)</term><term>Rats</term><term>Rats, Wistar</term><term>Sulfhydryl Compounds (metabolism)</term><term>brain</term><term>dihydroxybenzoic acid</term><term>dopamine</term><term>entacapone</term><term>levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Homocysteine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amino Acids</term><term>Catechol O-Methyltransferase</term><term>Homocysteine</term><term>Hydroxybenzoates</term><term>Sulfhydryl Compounds</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Astrocytes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Enzyme Activation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Chromatography, High Pressure Liquid</term><term>Rats</term><term>Rats, Wistar</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Elevation of the total homocysteine (tHcy) concentration in plasma has been implicated in neurodegeneration in patients with stroke, dementia, Alzheimer disease, and Parkinson disease. Because the mechanisms controlling brain tHcy are unknown, the present study investigated its synthesis and transport in primary rat brain cell cultures. We found that the catechol‐O‐methyltransferase (COMT) substrate 3,4‐dihydroxybenzoic acid (DHB) increased export of tHcy in astrocytes, but not in neurons. The export mechanism was selective for tHcy over cyst(e)ine, total glutathione (tGSH) or cysteinylglycine (Cys‐Gly). tHcy export from astrocytes was also induced by the COMT substrates levodopa (L‐DOPA), dopamine and quercetin, and it was blocked by the COMT inhibitors tropolone and entacapone. This export was associated with increased synthesis of tHcy because both intracellular and extracellular tHcy concentrations rose during COMT activation. Incubation in cyst(e)ine‐deficient medium inhibited the tHcy export response to COMT activation. Exogenous tHcy (100 μM) was accumulated into neurons, but not into astrocytes. We conclude that activation of COMT causes sustained synthesis of Hcy in astrocytes and transport of this amino acid to neurons.© 2005 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Canada</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>État de New York</li></region><settlement><li>Tianjin</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Huang, Guowei" sort="Huang, Guowei" uniqKey="Huang G" first="Guowei" last="Huang">Guowei Huang</name></noRegion><name sortKey="Dragan, Magdalena" sort="Dragan, Magdalena" uniqKey="Dragan M" first="Magdalena" last="Dragan">Magdalena Dragan</name><name sortKey="Freeman, David" sort="Freeman, David" uniqKey="Freeman D" first="David" last="Freeman">David Freeman</name><name sortKey="Wilson, John X" sort="Wilson, John X" uniqKey="Wilson J" first="John X." last="Wilson">John X. Wilson</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Huang, Guowei" sort="Huang, Guowei" uniqKey="Huang G" first="Guowei" last="Huang">Guowei Huang</name></noRegion></country><country name="États-Unis"><region name="État de New York"><name sortKey="Wilson, John X" sort="Wilson, John X" uniqKey="Wilson J" first="John X." last="Wilson">John X. Wilson</name></region><name sortKey="Wilson, John X" sort="Wilson, John X" uniqKey="Wilson J" first="John X." last="Wilson">John X. Wilson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002A87 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002A87 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:5E2166F0CF3B4D3560BB1C2549EB924AF069A302
|texte= Activation of catechol‐O‐methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons
}}
| This area was generated with Dilib version V0.6.29. |  |