RESUMEN
Cardiac tissue from autoimmune myocarditis mice was studied to evaluate the expression and biological activity of mRNA encoding H(1) receptor and iNOS. BALB/c inbred mice were immunized with heart protein and sacrificed at 20, 45 and 50 days post immunization. Heart contractility studies and RT-PCR assays were performed. Heart from autoimmune myocarditis mice show mRNA iNOS-related dysfunction with a decrease in heart contractility. This effect was accompanied with an increase production of cyclic GMP and was improved by treating autoimmune mice with an inhibitor of iNOS activity. In addition, autoimmune myocardium expressed an active histamine H(1) receptor mRNA coupled to phospholipase C. The activation of H(1) receptor by ThEA stimulated both phosphoinositide hydrolysis and heart contractility. Normal myocardium did not expressed neither iNOS mRNA nor H(1) receptor mRNA. In conclusions: the development of autoimmune cardiac dysfunction was associated with the expression of iNOS mRNA, cyclic GMP accumulation and the expression of an active histamine H(1) receptor mRNA with increase production of inositol phosphates. These protein emergence during the course of autoimmune myocarditis may be involved a distinct compensatory mechanism operating in this disease.
Asunto(s)
Miocarditis/metabolismo , Óxido Nítrico Sintasa/metabolismo , ARN Mensajero/metabolismo , Receptores Histamínicos H1/metabolismo , Animales , GMP Cíclico/metabolismo , Fosfatos de Inositol/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Contracción Miocárdica/inmunología , Miocarditis/enzimología , Miocarditis/inmunología , Radioinmunoensayo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This study reports the expression of the ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene (PFKFB3) (PFK-2/FBPase-2) in different stages of rat brain development. Northern blot and RT-PCR analysis demonstrated that ubiquitous PFK-2/FBPase-2 is expressed in rat brain from embryonic to adult life and shows a transient increase 1 day before birth, coincident with the maximum concentration of Fru-2,6-P(2) and PFK-2 activity. The levels of brain PFK-2/FBPase-2 gene expression as well as the enzymatic activity and the concentration of Fru-2,6-P(2) appear to be remarkably constant during adult life, without significant differences in the brain hippocampus, cortex, cerebellum or striatum areas.