The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes

Autor(es)

Bergantin, Leandro Bueno ^[1] ; Figueiredo, Leonardo Bruno ^[1] ; Godinho, Rosely Oliveira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Applied Physiology; v. 111, n. 6, p. 1710-1718, DEC 2011.
• Citações Web of Science: 4

Resumo

Bergantin LB, Figueiredo LB, Godinho RO. The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes. J Appl Physiol 111: 1710-1718, 2011. First published September 15, 2011; doi:10.1152/japplphysiol.00586.2011.-The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with beta-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. In conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes. (AU)

• Processo FAPESP: 08/55988-2 - Efeito da pentoxifilina e participacao da sinalizacao mediada pelo amp ciclico na atrofia e proteolise induzidas pela desnervacao de musculos esqueleticos
• Beneficiário: Leandro Bueno Bergantin
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 05/59006-1 - AMP cíclico intra e extracelular como sinalizador da sinapse neuromuscular esquelética: mecanismos de regulação
• Beneficiário: Rosely Oliveira Godinho
• Modalidade de apoio: Auxílio à Pesquisa - Regular