ParkinsonCanadaV1, Main, Exploration, bibRecord, 002B50

Activation of catechol-O-methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons

Identifieur interne : 002B50 ( Main/Exploration ); précédent : 002B49; suivant : 002B51

Activation 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 : (New York, NY. Print) [ 0894-1491 ] ; 2005.

RBID : Pascal:05-0297115

Descripteurs français

Pascal (Inist)
- Catechol O-methyltransferase, Astrocyte, Homocystéine, Biosynthèse, Neurone, Encéphale, Dopamine, Entacapone, Lévodopa, Cellule gliale, Système nerveux central.

English descriptors

KwdEn :
- Astrocyte, Biosynthesis, Catechol O-methyltransferase, Central nervous system, Dopamine, Encephalon, Entacapone, Glial cell, Homocystein, Levodopa, Neuron.

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.

Affiliations:

Links toward previous steps (curation, corpus...)

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to stream Main, to step Curation: 002B50

Le document en format XML

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<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.</div>
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Activation of catechol-O-methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons

Activation of catechol-O-methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri