RESUMO
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.
Assuntos
Adenosina Trifosfatases/biossíntese , Adenosina Trifosfatases/genética , Química Encefálica/efeitos dos fármacos , Encéfalo/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Prolina/toxicidade , Peixe-Zebra/metabolismo , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Membranas/efeitos dos fármacos , Membranas/metabolismo , Pirofosfatases/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas de Peixe-Zebra/metabolismoRESUMO
Pyroglutamyl proline-rich oligopeptides, present in the venom of the pit viper Bothrops jararaca (Bj-PROs), are the first described naturally occurring inhibitors of the angiotensin I-converting enzyme (ACE). The inhibition of ACE by the decapeptide Bj-PRO- 10c (Assuntos
Animais
, Bothrops
, Prolina/antagonistas & inibidores
, Prolina/toxicidade
, Venenos de Serpentes/antagonistas & inibidores
, Venenos de Serpentes/toxicidade
RESUMO
We have previously demonstrated that acute and chronic hyperprolinemia induce oxidative stress in cerebral cortex of rats. In the present study, we investigated the action of Vitamins E and C on the oxidative damage elicited by acute and chronic administration of proline (Pro) in rat cerebral cortex. Results showed that treatment with Vitamins E and C prevented the alterations caused by acute and chronic administration of proline on chemiluminescence, total radical-trapping antioxidant potential (TRAP) and on the activities of catalase and glutathione peroxidase. If these effects also occur in the human condition, it is possible that antioxidant administration might serve as a potential adjuvant therapy to avoid the progression of the neuropsychiatric dysfunction observed in hyperprolinemic patients.