The kinin B-1 receptor regulates muscle-specific E3 ligases expression and is involved in skeletal muscle mass control

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dc.contributor.authorParreiras-e-Silva, Lucas T.
dc.contributor.authorReis, Rosana I.
dc.contributor.authorSantos, Geisa A.
dc.contributor.authorPires-Oliveira, Marcelo [UNIFESP]
dc.contributor.authorPesquero, Joao B. [UNIFESP]
dc.contributor.authorGomes, Marcelo D.
dc.contributor.authorGodinho, Rosely O. [UNIFESP]
dc.contributor.authorCosta-Neto, Claudio M.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:37:41Z
dc.date.available2016-01-24T14:37:41Z
dc.date.issued2014-08-01
dc.description.abstractRegulation of muscle mass depends on the balance between synthesis and degradation of proteins, which is under the-control of different signalling pathways regulated by hormonal, neural and nutritional stimuli. Such stimuli are altered in several pathologies, including COPD (chronic obstructive pulmonary disease), diabetes, AIDS and cancer (cachexia), as well as in some conditions such as immobilization and aging (sarcopenia), leading to muscle atrophy, which represents a significant contribution to patient morbidity. the KKS (kallikrein kinin system) is composed of the enzymes kallikreins, which generate active peptides called kinins that activate two G-protein-coupled receptors, namely B-1 and B-2, which are expressed in a variety of tissues. the local modulation of the KKS may account for its participation in different diseases, such as those of the cardiovascular, renal and central nervous systems, cancer and many inflammatory processes, including pain. Owing to such pleiotropic actions of the KKS by local modulatory events and the probable fine-tuning of associated signalling cascades involved in skeletal muscle catabolic disorders [for example, NF-kappa B (nuclear factor kappa B) and PI3K (phosphoinositide 3-kinase)/Akt pathways], we hypothesized that KKS might contribute to the modulation of intracellular responses in atrophying skeletal muscle. Our results show that kinin B-1 receptor activation induced a decrease in the diameter of C2C12 myotubes, activation of NF-kappa B, a decrease in Akt phosphorylation levels, and an increase in the mRNA levels of the ubiquitin E3 ligases atrogin-1 and MuRF-1 (muscle RING-finger protein-1). in vivo, we observed an increase in kinin B-1 receptor mRNA levels in an androgen-sensitive model of muscle atrophy. in the same model, inhibition of the kinin B-1 receptor with a selective antagonist resulted in an impairment of atrogin-1 and MuRF-1 expression and I kappa B (inhibitor of NF-kappa B) phosphorylation. Moreover, knockout of the kinin B-1 receptor in mice led to an impairment in MuRF-1 mRNA expression after induction of LA (levator ani) muscle atrophy. in conclusion, using pharmacological and gene-ablation tools, we have obtained evidence that the kinin B-1 receptor plays a significant role in the regulation of skeletal muscle proteolysis in the LA muscle atrophy model.en
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Ctr Integrat Syst Biol CISBi, BR-14049900 Ribeirao Preto, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04039032 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent185-194
dc.identifierhttp://dx.doi.org/10.1042/CS20130358
dc.identifier.citationClinical Science. London: Portland Press Ltd, v. 127, n. 3-4, p. 185-194, 2014.
dc.identifier.doi10.1042/CS20130358
dc.identifier.issn0143-5221
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38060
dc.identifier.wosWOS:000339225900005
dc.language.isoeng
dc.publisherPortland Press Ltd
dc.relation.ispartofClinical Science
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectG-protein-coupled receptor (GPCR)en
dc.subjectkinin B-1 receptoren
dc.subjectmuscle atrophyen
dc.subjectprotein metabolismen
dc.subjectsignal transductionen
dc.subjectubiquitin-proteasome systemen
dc.titleThe kinin B-1 receptor regulates muscle-specific E3 ligases expression and is involved in skeletal muscle mass controlen
dc.typeinfo:eu-repo/semantics/article
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