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

Detalhes bibliográficos
Autor(a) principal: Bergantin, Leandro Bueno [UNIFESP]
Data de Publicação: 2011
Outros Autores: Figueiredo, Leonardo Bruno [UNIFESP], Godinho, Rosely Oliveira [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1152/japplphysiol.00586.2011
http://repositorio.unifesp.br/handle/11600/34258
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.
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spelling The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposesprotein degradationtyrosine releasemuscle atrophyubiquitin-proteasomecalpainBergantin 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.Universidade Federal de São Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP: 05/59006-1FAPESP: 08/55988-2CNPq: 304602/2008-6Amer Physiological SocUniversidade Federal de São Paulo (UNIFESP)Bergantin, Leandro Bueno [UNIFESP]Figueiredo, Leonardo Bruno [UNIFESP]Godinho, Rosely Oliveira [UNIFESP]2016-01-24T14:17:29Z2016-01-24T14:17:29Z2011-12-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion1710-1718http://dx.doi.org/10.1152/japplphysiol.00586.2011Journal of Applied Physiology. Bethesda: Amer Physiological Soc, v. 111, n. 6, p. 1710-1718, 2011.10.1152/japplphysiol.00586.20118750-7587http://repositorio.unifesp.br/handle/11600/34258WOS:000298346100027engJournal of Applied Physiologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2022-11-03T15:00:26Zoai:repositorio.unifesp.br/:11600/34258Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-11-03T15:00:26Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
title The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
spellingShingle The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
Bergantin, Leandro Bueno [UNIFESP]
protein degradation
tyrosine release
muscle atrophy
ubiquitin-proteasome
calpain
title_short The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
title_full The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
title_fullStr The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
title_full_unstemmed The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
title_sort The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
author Bergantin, Leandro Bueno [UNIFESP]
author_facet Bergantin, Leandro Bueno [UNIFESP]
Figueiredo, Leonardo Bruno [UNIFESP]
Godinho, Rosely Oliveira [UNIFESP]
author_role author
author2 Figueiredo, Leonardo Bruno [UNIFESP]
Godinho, Rosely Oliveira [UNIFESP]
author2_role author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Bergantin, Leandro Bueno [UNIFESP]
Figueiredo, Leonardo Bruno [UNIFESP]
Godinho, Rosely Oliveira [UNIFESP]
dc.subject.por.fl_str_mv protein degradation
tyrosine release
muscle atrophy
ubiquitin-proteasome
calpain
topic protein degradation
tyrosine release
muscle atrophy
ubiquitin-proteasome
calpain
description 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.
publishDate 2011
dc.date.none.fl_str_mv 2011-12-01
2016-01-24T14:17:29Z
2016-01-24T14:17:29Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1152/japplphysiol.00586.2011
Journal of Applied Physiology. Bethesda: Amer Physiological Soc, v. 111, n. 6, p. 1710-1718, 2011.
10.1152/japplphysiol.00586.2011
8750-7587
http://repositorio.unifesp.br/handle/11600/34258
WOS:000298346100027
url http://dx.doi.org/10.1152/japplphysiol.00586.2011
http://repositorio.unifesp.br/handle/11600/34258
identifier_str_mv Journal of Applied Physiology. Bethesda: Amer Physiological Soc, v. 111, n. 6, p. 1710-1718, 2011.
10.1152/japplphysiol.00586.2011
8750-7587
WOS:000298346100027
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Applied Physiology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1710-1718
dc.publisher.none.fl_str_mv Amer Physiological Soc
publisher.none.fl_str_mv Amer Physiological Soc
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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