Long-term proline exposure alters nucleotide catabolism and ectonucleotidase gene expression in zebrafish brain.
Metab Brain Dis
; 27(4): 541-9, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-22669495
Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures cognitive dysfunctions, and psychotic disorders. However, the underlying mechanisms of these symptoms are still unclear. Since adenine nucleotides play crucial roles in neurotransmission and neuromodulation, we evaluated the in vivo and in vitro effects of proline on ectonucleotidase activities and gene expression in zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0 mM) during 1 h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 µM) were tested. Short-term proline exposure did not promote significant changes on the ectonucleotidase activities and gene expression. Long-term proline exposure significantly increased ATP catabolism in both concentrations tested (14 % and 22 %, respectively), whereas ADP and AMP hydrolysis were increased only at 3.0 mM proline (21 % and 17 %, respectively) when compared to control. Moreover, the relative gene expression of enpd3 increased in both treated groups after long-term proline, whereas enptd1 increased only at 3.0 mM proline. Proline in vitro did not promote significant changes on ectonucleotidase activities. Altogether, these data indicate that the enzymes responsible for the control of extracellular nucleotides levels might be altered after proline exposure in zebrafish, contributing to better understand the pathophysiology of this disease. Moreover, such findings might facilitate the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Encéfalo
/
Química Encefálica
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Prolina
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Regulação Enzimológica da Expressão Gênica
/
Adenosina Trifosfatases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Metab Brain Dis
Assunto da revista:
CEREBRO
/
METABOLISMO
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos