RESUMO
AIM: This study aimed to investigate the effects of caffeine on pathways associated with mitochondrial quality control and mitochondrial capacity during skeletal muscle regeneration, focusing on the role of Parkin, a key protein involved in mitophagy. METHODS: We used in vitro C2C12 myoblast during differentiation with and without caffeine in the medium, and we evaluated several markers of mitochondrial quality control pathways and myotube growth. In vivo experiments, we used C57BL/6J (WT) and Parkintm 1Shn lineage (Parkin-/- ) mice and injured tibial anterior muscle. The mice regenerated TA muscle for 3, 10, and 21 days with or without caffeine ingestion. TA muscle was used to analyze the protein content of several markers of mitochondrial quality pathways, muscle satellite cell differentiation, and protein synthesis. Furthermore, it analyzed mtDNA, mitochondrial respiration, and myofiber growth. RESULTS: C2C12 differentiation experiments showed that caffeine decreased Parkin content, potentially leading to increased DRP1 and PGC-1α content and altered mitochondrial population, thereby enhancing growth capacity. Using Parkin-/- mice, we found that caffeine intake during the regenerative process induces an increase in AMPKα phosphorylation and PGC-1α and TFAM content, changes that were partly Parkin-dependent. In addition, the absence of Parkin potentiates the ergogenic effect of caffeine by increasing mitochondrial capacity and myotube growth. Those effects are related to increased ATF4 content and activation of protein synthesis pathways, such as increased 4E-BP1 phosphorylation. CONCLUSION: These findings demonstrate that caffeine ingestion changes mitochondrial quality control during skeletal muscle regeneration, and Parkin is a central player in those mechanisms.
Assuntos
Cafeína , Músculo Esquelético , Camundongos , Animais , Cafeína/farmacologia , Músculo Esquelético/metabolismo , Camundongos Endogâmicos C57BL , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , RegeneraçãoRESUMO
Fibroblasts are a highly heterogeneous population of cells, being found in a large number of different tissues. These cells produce the extracellular matrix, which is essential to preserve structural integrity of connective tissues. Fibroblasts are frequently engaged in migration and remodeling, exerting traction forces in the extracellular matrix, which is crucial for matrix deposition and wound healing. In addition, previous studies performed on primary myoblasts suggest that the E3 ligase MuRF2 might function as a cytoskeleton adaptor. Here, we hypothesized that MuRF2 also plays a functional role in skeletal muscle fibroblasts. We found that skeletal muscle fibroblasts express MuRF2 and its siRNA knock-down promoted decreased fibroblast migration, cell border accumulation of polymerized actin, and down-regulation of the phospho-Akt expression. Our results indicated that MuRF2 was necessary to maintain the actin cytoskeleton functionality in skeletal muscle fibroblasts via Akt activity and exerted an important role in extracellular matrix remodeling in the skeletal muscle tissue.
Assuntos
Animais , Ratos , Diferenciação Celular/fisiologia , Músculo Esquelético/fisiologia , Ubiquitina-Proteína Ligases/fisiologia , Proliferação de Células/fisiologia , Fibroblastos/fisiologia , Proteínas Musculares/fisiologia , Western Blotting , Imunofluorescência , Músculo Esquelético/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Fibroblastos/metabolismo , Proteínas Musculares/metabolismoRESUMO
Este trabalho tem por objetivo apresentar uma descrição dos procedimentos necessários para montagem, instalação e manutenção de um quarto de iodoterapia, tendo como meta principal uma melhor relação entre os fatores: necessidades do paciente e adequação com as normas de proteção radiológica estabelecidas pela Comissão Nacional de Energia Nuclear.
This articles has the objective to show the description of rules necessaries to assemble, to installation and mainterence the iodotherapy's room; and having the principal aim, get a better relacion between the factors: necessities of the pacient and the adaptation with the norms of protection radiologic established by the National Comission Nuclear Energy.