RGD Reference Report - Activation of catechol-O-methyltransferase in astrocytes stimulates homocysteine synthesis and export to neurons. - Rat Genome Database

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

Authors: Huang, G  Dragan, M  Freeman, D  Wilson, JX 
Citation: Huang G, etal., Glia. 2005 Jul;51(1):47-55.
RGD ID: 2289784
Pubmed: PMID:15779086   (View Abstract at PubMed)
DOI: DOI:10.1002/glia.20185   (Journal Full-text)

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 muM) 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of homocysteine metabolic process  IMP 2289784 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Comt  (catechol-O-methyltransferase)


Additional Information