Expression of glutamate carboxypeptidase II in human brain
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
17150306
DOI
10.1016/j.neuroscience.2006.10.022
PII: S0306-4522(06)01367-4
Knihovny.cz E-zdroje
- MeSH
- aktivace enzymů fyziologie MeSH
- antigeny povrchové analýza imunologie metabolismus MeSH
- astrocyty enzymologie MeSH
- dipeptidy metabolismus MeSH
- glutamátkarboxypeptidasa II analýza imunologie metabolismus MeSH
- imunohistochemie metody MeSH
- kyselina glutamová biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mapování epitopu metody MeSH
- molekulární modely MeSH
- mozek anatomie a histologie enzymologie MeSH
- protilátky imunologie MeSH
- radioligandová zkouška metody MeSH
- rekombinantní fúzní proteiny metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- terciární struktura proteinů fyziologie MeSH
- western blotting MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny povrchové MeSH
- dipeptidy MeSH
- FOLH1 protein, human MeSH Prohlížeč
- glutamátkarboxypeptidasa II MeSH
- isospaglumic acid MeSH Prohlížeč
- kyselina glutamová MeSH
- protilátky MeSH
- rekombinantní fúzní proteiny MeSH
Glutamate carboxypeptidase II (GCPII) is a transmembrane glycoprotein expressed in various tissues. When expressed in the brain it cleaves the neurotransmitter N-acetylaspartylglutamate (NAAG), yielding free glutamate. In jejunum it hydrolyzes folylpoly-gamma-glutamate, thus facilitating folate absorption. The prostate form of GCPII, known as prostate specific membrane antigen (PSMA), is an established cancer marker. The NAAG-hydrolyzing activity of GCPII has been implicated in a number of pathological conditions in which glutamate is neurotoxic (e.g. amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, epilepsy, schizophrenia, and stroke). Inhibition of GCPII was shown to be neuroprotective in tissue culture and in animal models. GCPII is therefore an interesting putative therapeutic target. However, only very limited and controversial data on the expression and localization of GCPII in human brain are available. Therefore, we set out to analyze the activity and expression of GCPII in various compartments of the human brain using a radiolabeled substrate of the enzyme and the novel monoclonal antibody GCP-04, which recognizes an epitope on the extracellular portion of the enzyme and is more sensitive to GCPII than to the homologous GCPIII. We show that this antibody is more sensitive in immunoblots than the widely used antibody 7E11. By Western blot, we show that there are approximately 50-300 ng of GCPII/mg of total protein in human brain, depending on the specific area. Immunohistochemical analysis revealed that astrocytes specifically express GCPII in all parts of the brain. GCPII is enzymatically active and the level of activity follows the expression pattern. Using pure recombinant GCPII and homologous GCPIII, we conclude that GCPII is responsible for the majority of overall NAAG-hydrolyzing activity in the human brain.
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