Abstract
In contrast to carbohydrate and lipid metabolism, much little is known about the neural, hormonal and nutritional control of protein metabolism in skeletal muscle. Therefore, the main goal of the present project is to investigate the central and peripheral mechanisms by which the Central Nervous System, via sympathetic stimulation, controls the rate of protein metabolism in rat skeletal muscle. More specifically, our goal is to describe the mechanisms (signaling pathway, transcription factors, protein degradation and protein synthesis pathways, etc.) involved in the anabolic and antiatrophy effect promoted by stimulation of b2-adrenoceptors and cAMP in skeletal muscle. Also, we propose to investigate the role of hypothalamus as the neural center that regulates the metabolic actions of catecholamines in skeletal muscle. For this, we will study the intracellular events that take part in the alterations of skeletal muscle protein metabolism in experimental models of sympathetic hyperactivity during short (intracerebroventricular injections of neostigmine, 2-DG or C75) and long periods (chronic intermittent hypoxia). Understanding the signaling and neural pathways that regulate muscle mass provide potential therapeutic targets for the prevention and treatment of muscle wasting in metabolic and neuromuscular diseases. (AU)
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