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The kinin B1 receptor regulates muscle-specific E3 ligases expression and is involved in skeletal muscle mass control.
Clin Sci (Lond). 2014 Aug; 127(3):185-94.CS

Abstract

Regulation 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 B1 and B2, 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-κB (nuclear factor κB) 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 B1 receptor activation induced a decrease in the diameter of C2C12 myotubes, activation of NF-κB, 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 B1 receptor mRNA levels in an androgen-sensitive model of muscle atrophy. In the same model, inhibition of the kinin B1 receptor with a selective antagonist resulted in an impairment of atrogin-1 and MuRF-1 expression and IκB (inhibitor of NF-κB) phosphorylation. Moreover, knockout of the kinin B1 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 B1 receptor plays a significant role in the regulation of skeletal muscle proteolysis in the LA muscle atrophy model.

Authors+Show Affiliations

*Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.*Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.*Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.†Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, 04039-032 São Paulo, SP, Brazil.‡Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, 04039-032 São Paulo, SP, Brazil.*Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.†Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, 04039-032 São Paulo, SP, Brazil.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24498923

Citation

Parreiras-E-Silva, Lucas T., et al. "The Kinin B1 Receptor Regulates Muscle-specific E3 Ligases Expression and Is Involved in Skeletal Muscle Mass Control." Clinical Science (London, England : 1979), vol. 127, no. 3, 2014, pp. 185-94.
Parreiras-E-Silva LT, Reis RI, Santos GA, et al. The kinin B1 receptor regulates muscle-specific E3 ligases expression and is involved in skeletal muscle mass control. Clin Sci. 2014;127(3):185-94.
Parreiras-E-Silva, L. T., Reis, R. I., Santos, G. A., Pires-Oliveira, M., Pesquero, J. B., Gomes, M. D., Godinho, R. O., & Costa-Neto, C. M. (2014). The kinin B1 receptor regulates muscle-specific E3 ligases expression and is involved in skeletal muscle mass control. Clinical Science (London, England : 1979), 127(3), 185-94. https://doi.org/10.1042/CS20130358
Parreiras-E-Silva LT, et al. The Kinin B1 Receptor Regulates Muscle-specific E3 Ligases Expression and Is Involved in Skeletal Muscle Mass Control. Clin Sci. 2014;127(3):185-94. PubMed PMID: 24498923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The kinin B1 receptor regulates muscle-specific E3 ligases expression and is involved in skeletal muscle mass control. AU - Parreiras-E-Silva,Lucas T, AU - Reis,Rosana I, AU - Santos,Geisa A, AU - Pires-Oliveira,Marcelo, AU - Pesquero,João B, AU - Gomes,Marcelo D, AU - Godinho,Rosely O, AU - Costa-Neto,Claudio M, PY - 2014/2/7/entrez PY - 2014/2/7/pubmed PY - 2014/6/10/medline SP - 185 EP - 94 JF - Clinical science (London, England : 1979) JO - Clin. Sci. VL - 127 IS - 3 N2 - Regulation 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 B1 and B2, 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-κB (nuclear factor κB) 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 B1 receptor activation induced a decrease in the diameter of C2C12 myotubes, activation of NF-κB, 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 B1 receptor mRNA levels in an androgen-sensitive model of muscle atrophy. In the same model, inhibition of the kinin B1 receptor with a selective antagonist resulted in an impairment of atrogin-1 and MuRF-1 expression and IκB (inhibitor of NF-κB) phosphorylation. Moreover, knockout of the kinin B1 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 B1 receptor plays a significant role in the regulation of skeletal muscle proteolysis in the LA muscle atrophy model. SN - 1470-8736 UR - https://www.unboundmedicine.com/medline/citation/24498923/The_kinin_B1_receptor_regulates_muscle_specific_E3_ligases_expression_and_is_involved_in_skeletal_muscle_mass_control_ L2 - https://portlandpress.com/clinsci/article-lookup/doi/10.1042/CS20130358 DB - PRIME DP - Unbound Medicine ER -