Oxytocin induces anti-catabolic and anabolic effects on protein metabolism in the female rat oxidative skeletal muscle
Autor: | Danilo Lustrino, Sandra Lauton-Santos, Daniel Badaue-Passos, João da Cruz-Filho, Luiz Carlos Carvalho Navegantes, João Victor Gomes-Santos, Neusa Maria Zanon, Alan Bruno Silva Vasconcelos, Waldecy de Lucca, Enilton A. Camargo, Isis do Carmo Kettelhut, Luís Carlos Reis, André S. Mecawi, Daniely Messias Costa |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Protein metabolism FOXO1 Stimulation Oxytocin 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Anabolic Agents 0302 clinical medicine Oxytocics Internal medicine medicine Animals Rats Wistar General Pharmacology Toxicology and Pharmaceutics Muscle Skeletal Receptor Protein kinase B Soleus muscle Chemistry Skeletal muscle General Medicine medicine.disease Rats Oxidative Stress 030104 developmental biology Endocrinology medicine.anatomical_structure Protein Biosynthesis Sarcopenia Proteolysis Female Lysosomes TRANSDUÇÃO DE SINAL CELULAR Signal Transduction |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 0024-3205 |
DOI: | 10.1016/j.lfs.2021.119665 |
Popis: | Aims Although it is well established that skeletal muscle contains oxytocin (OT) receptors and OT-knockout mice show premature development of sarcopenia, the role of OT in controlling skeletal muscle mass is still unknown. Therefore, the present work aimed to determine OT's effects on skeletal muscle protein metabolism. Main methods Total proteolysis, proteolytic system activities and protein synthesis were assessed in isolated soleus muscle from prepubertal female rats. Through in vivo experiments, rats received 3-day OT treatment (3UI.kg−1.day−1, i.p.) or saline, and muscles were harvested for mass-gain assessment. Key findings In vitro OT receptor stimulation reduced total proteolysis, specifically through attenuation of the lysosomal and proteasomal proteolytic systems, and in parallel activated the Akt/FoxO1 signaling and suppressed atrogenes (e.g., MuRF-1 and atrogin-1) expression induced by motor denervation. On the other hand, the protein synthesis was not altered by in vitro treatment with the OT receptor-selective agonist. Although short-term OT treatment did not change the atrogene mRNA levels, the protein synthesis was stimulated, resulting in soleus mass gain, probably through an indirect effect. Significance Taken together, these data show for the first time that OT directly inhibits the proteolytic activities of the lysosomal and proteasomal systems in rat oxidative skeletal muscle by suppressing atrogene expression via stimulation of Akt/FoxO signaling. Moreover, the data obtained from in vivo experiments suggest OT's ability to control rat oxidative skeletal muscle mass. |
Databáze: | OpenAIRE |
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