RESUMO
During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.
Assuntos
Glicogênio Sintase/metabolismo , Proteína Quinase 12 Ativada por Mitógeno/metabolismo , Proteína Quinase 13 Ativada por Mitógeno/metabolismo , Miocárdio/enzimologia , Animais , Animais Recém-Nascidos , Cardiomegalia/enzimologia , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Dieta Hiperlipídica , Ativação Enzimática , Comportamento Alimentar , Feminino , Deleção de Genes , Intolerância à Glucose/enzimologia , Glicogênio/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/enzimologia , Especificidade de Órgãos , FosforilaçãoRESUMO
Hepatitis C virus (HCV) infection remains a global health problem, detected only in the early stages by molecular tests. Molecular tests detect HCV RNA, which is very prone to degradation by ribonucleases, reason why blood samples must be transported and stored at - 20 °C, or even - 70 °C for long-term storage. Flinders Technology Associates (FTA) cards are a useful sampling collecting device for dry blood spot (DBS) storage, especially for low and middle-income countries (LMIC). In this study, we analyzed viral HCV RNA integrity for long-term storage at room temperature compared to - 20 °C using two different types of cards for DBS: FTA Classic and 903 Protein Saver cards. For this purpose, DBS were prepared on these cards using blood or plasma samples from HCV infected patients, and samples were analysed by conventional RT-PCR. Our results showed that 903 Protein Saver cards are the best and cheapest alternative for DBS storage at room temperature. In these conditions, we found that HCV RNA integrity lasted for up to 9 months.