Secretion of adenylate kinase 1 is required for extracellular ATP synthesis in C2C12 myotubes

Extracellular ATP (exATP) has been known to be a critical ligand regulating skeletal muscle differentiation and contractibility. ExATP synthesis was greatly increased with the high level of adenylate kinase 1 (AK1) and ATP synthase beta during C2C12 myogenesis. The exATP synthesis was abolished by the knock-down of AK1 but not by that of ATP synthase beta in C2C12 myotubes, suggesting that AK1 is required for exATP synthesis in myotubes. However, membrane-bound AK1beta was not involved in exATP synthesis because its expression level was decreased during myogenesis in spite of its localization in the lipid rafts that contain various kinds of receptors and mediate cell signal transduction, cell migration, and differentiation. Interestingly, cytoplasmic AK1 was secreted from C2C12 myotubes but not from C2C12 myoblasts. Taken together all these data, we can conclude that AK1 secretion is required for the exATP generation in myotubes.

The role of AMP kinase in diabetes.

Type 2 diabetes is characterized by abnormal metabolism of glucose and fat, due in part to resistance to the actions of insulin in peripheral tissues. If untreated it leads to several complications such as blindness, kidney failure, neuropathy and amputations. The benefit of exercise in diabetic patients is well known and recent research indicates that AMP activated protein kinase (AMPK) plays a major role in this exercise related effect. AMPK is considered as a master switch regulating glucose and lipid metabolism. The AMPK is an enzyme that works as a fuel gauge, being activated in conditions of high energy phosphate depletion. AMPK is also activated robustly by skeletal muscle contraction and myocardial ischaemia, and is involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and decreased production of glucose, cholesterol, and triglycerides. The two leading diabetic drugs namely, metformin and rosiglitazone, show their metabolic effects partially through AMPK. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.

Matabolismo energético durante el desarrollo de la placenta en ratas: efecto de la desnutrición materna crónica / Energy metabolism during placental development in rats-effect of chronic maternal malnutrition

Se estudió el efecto de la desnutricion crónica materna en el metabolismo enerético durante el desarrollo de la placenta en ratas y su relación con el crecimiento fetal. Ratas hembras vírgines de la cepa Wistar se sosmetieron a la restricción de una dieta con 25% de caseína, desde la pubertad y durante la preñez. Los resultados revelaron que la desnutrición materna disminuye significativamente la actividad de adenilato kinasa expresada pr gramo de DNA, y aumenta significativamente el contenido de adenina nucleótidios (ATP y ADP) en la placenta, cerca del término de la preñez. Se postula que el aumento significativo de la carga energética (ATP + 1/2 ADP:/ ATP + AMP) de la placenta de ratas desnutridas, es el resultado de una inhibición de los sistemas que utilizan ATP para procesos de síntesis de macromoléculas y transporte activo de sustratos en las últimas etapas de la gestación. Ello coincide con la significativa disminución del crecimiento fetal en esa etapa

Alteraçöes enzimáticas eritrocitárias na hemofilia A / Erythrocyte enzymatic changes in hemophilia A

Cinco quinases eritrocitárias foram estudadas em pacientes portadores de hemofilia A; foi encontrado um aumento das atividades da fosfogliceratoquinase e da adenilatoquinase. Este achado sugere que há alteraçöes metabólicas eritrocitárias na hemofilia