Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biochem J ; 449(1): 133-42, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23009292

RESUMO

DMD (Duchenne muscular dystrophy) is an incurable rapidly worsening neuromuscular degenerative disease caused by the absence of dystrophin. In skeletal muscle a lack of dystrophin disrupts the recruitment of neuronal NOS (nitric oxide synthase) to the sarcolemma thus affecting NO (nitric oxide) production. Utrophin is a dystrophin homologue, the expression of which is greatly up-regulated in the sarcolemma of dystrophin-negative fibres from mdx mice, a mouse model of DMD. Although cardiomyopathy is an important cause of death, little is known about the NO signalling pathway in the cardiac muscle of DMD patients. Thus we used cardiomyocytes and hearts from two month-old mdx and mdx:utrophin-/- (double knockout) mice (mdx:utr) to study key steps in NO signalling: L-arginine transporters, NOS and sGC (soluble guanylyl cyclase). nNOS did not co-localize with dystrophin or utrophin to the cardiomyocyte membrane. Despite this nNOS activity was markedly decreased in both mdx and mdx:utr mice, whereas nNOS expression was only decreased in mdx:utr mouse hearts, suggesting that utrophin up-regulation in cardiomyocytes maintains nNOS levels, but not function. sGC protein levels and activity remained at control levels. Unexpectedly, L-arginine transporter expression and function were significantly increased, suggesting a novel biochemical compensatory mechanism of the NO pathway and a potential entry site for therapeutics.


Assuntos
Arginina/metabolismo , Transportador 1 de Aminoácidos Catiônicos/biossíntese , Transportador 2 de Aminoácidos Catiônicos/biossíntese , Distrofia Muscular de Duchenne/metabolismo , Óxido Nítrico/fisiologia , Transdução de Sinais/genética , Regulação para Cima/genética , Sistemas de Transporte de Aminoácidos , Animais , Transportador 1 de Aminoácidos Catiônicos/genética , Transportador 2 de Aminoácidos Catiônicos/genética , Feminino , Masculino , Camundongos , Camundongos Endogâmicos mdx , Camundongos Knockout , Camundongos Transgênicos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Transporte Proteico/genética , Utrofina/biossíntese , Utrofina/deficiência , Utrofina/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...