The inhibitory role of sympathetic nervous system in the Ca2+-dependent proteolysis of skeletal muscle.
Mammalian cells contain several proteolytic systems to carry out the degradative processes and complex regulatory mechanisms to prevent excessive protein breakdown. Among these systems, the Ca2+-activated proteolytic system involves the cysteine proteases denoted calpains, and their inhibitor, calpastatin. Despite the rapid progress in molecular research on calpains and calpastatin, the physiological role and regulatory mechanisms of these proteins remain obscure. Interest in the adrenergic effect on Ca2+-dependent proteolysis has been stimulated by the finding that the administration of beta2-agonists induces muscle hypertrophy and prevents the loss of muscle mass in a variety of pathologic conditions in which calpains are activated. This review summarizes evidence indicating that the sympathetic nervous system produces anabolic, protein-sparing effects on skeletal muscle protein metabolism. Studies are reviewed, which indicate that epinephrine secreted by the adrenal medulla and norepinephrine released from adrenergic terminals have inhibitory effects on Ca2+-dependent protein degradation, mainly in oxidative muscles, by increasing calpastatin levels. Evidence is also presented that this antiproteolytic effect, which occurs under both basal conditions and in stress situations, seems to be mediated by beta2- and beta3-adrenoceptors and cAMP-dependent pathways. The understanding of the precise mechanisms by which catecholamines promote muscle anabolic effects may have therapeutic value for the treatment of muscle-wasting conditions and may enhance muscle growth in farm species for economic and nutritional purposes.
Navegantes
L C C
LC
Departamento de Fisiologia, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP, Brazil. navegantes@fmrp.usp.br
Baviera
A M
AM
Kettelhut
I C
IC
D000313:Adrenal Medulla / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; D009124:Muscle Proteins; C033668:calpastatin; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine