ABSTRACT
Abstract Introduction: Recent studies have pointing creatine supplementation as a promising therapeutic alterna- tive in several diseases, especially myopathies and neurodegenerative disorder. Objective: elucidate the role of creatine supplementation on deleterious effect caused by limb immobilization in humans and rats. Methods: Analyzed articles were searched by three online databases, PubMed, SportDicus e Scielo. After a review and analysis, the studies were included in this review articles on effect of creatine supplementation on skeletal muscle in humans and rat, before, during and after a period of limb immobilization. Results: Studies analyzed demonstrated positive points in use of creatine supplementation as a therapeutic tool to mitigating the deleterious effects of limb immobilization, in humans and rat. Conclusion: The dataset of this literature review allows us to conclude that creatine supplementation may reduce muscle loss and/or assist in the recovery of muscle atrophy caused by immobilization and disuse in rats and humans. Also, we note that further research with better methodological rigor is needed to clarify the mechanisms by which creatine support the recovery of muscle atrophy. Moreover, these effects are positive and promising in the field of muscle rehabilitation, especially after member's immobilization.
Resumo Introdução: Estudos recentes apontam a suplementação de creatina como promissora alternativa terapêuti- ca em desordens de diversos tipos, especialmente miopatias e desordens neurodegenerativas. Objetivo: Essa revisão tem o objetivo de elucidar o papel da creatina sobre a perda da massa muscular causada pela imobili- zação de membros em seres humanos e ratos. Métodos: Os artigos analisados foram buscados em três bases de dados on-line, PubMed, SportDiscus e Scielo. Após análise dos estudos, foram incluídos na presente revisão os efeitos da suplementação de creatina na musculatura esquelética, envolvendo seres humanos e roedores, antes, durante e depois de um período de imobilização e desuso. Resultados: Os estudos analisados apresentaram pontos positivos sobre a utilização de creatina, sobretudo quando combinado com outro recurso terapêutico, atenuando a atrofia muscular causada pela imobilização de membros. Conclusão: Em suma, o conjunto de dados ainda que limitantes apresentado por essa revisão de literatura nos permite concluir que a suplemen- tação com creatina é capaz de amenizar a perda de massa muscular e/ou auxiliar na recuperação da atrofia muscular causada pela imobilização e desuso em ratos e humanos. Ainda, salientamos que mais investigações com melhor rigor metodológico são necessárias para o esclarecimento sobre os mecanismos pelo qual a creati- na favorece a recuperação da atrofia muscular. Alem disso, esses efeitos são positivos e promissores na área da reabilitação muscular, especialmente após a imobilização de membros.
Subject(s)
Humans , Animals , Muscular Atrophy , Creatine , Immobilization , Muscle, Skeletal , Muscular DiseasesABSTRACT
Objective To confirm whether fasudil can block C2C12 myoblasts respiration dysfunction triggered by Rho-associated coiled-coil containing protein kinase 1 (ROCK1), and whether it can block the occurrence of muscle atrophy. Methods C2C12 myoblasts were cultured in vitro, and 2% horse serum was used to induce cell differentiation and maturation. The obtained mature muscle tubule cells were divided into four groups according to the different stimuli: Ad-GFP group, only transfected GPT-adenovirus vector (Adv) in C2C12 myoblasts; Ad-ROCKl group, transfected ROCKl-Adv in C2C12 myoblasts to induce ROCK1 overexpression; Ad-GFPF group, transfected GFP-Adv and given 10 μmol/L fasudil in C2C12 myoblasts; and Ad-ROCKIF group, transfected ROCKl-Adv and given 10 μmol/L fasudil in C2C12 myoblasts. The oxygen consumption rate (OCR) and extracelluar acidification rate (ECAR) of C2C12 myoblasts under different stimulation conditions were evaluated by cell energy metabolism analyzer (Seahorse), so as to determine the effect of ROCK1 overexpression and fasudil stimulation on the respiratory function of C2C12 myoblasts. Mitochondrial fission was measured by MitoTracker® red fluorescent probes. The expressions of ROCK1, mitochondrial related protein 1 (Drpl) and phosphorylated p-Drpl, E3 ubiquitin ligase muscle RING finger-1 protein (MuRFl) and muscle atrophy F-box (MAFbx, Atrogin 1) was measured by Western blotting analysis. Results Seahorse analysis showed that the OCR, ECAR, basal respiration, maximal respiration and respiration required for coupling ATP of C2C12 myoblasts in the Ad ROCK1 group were significantly increased compared with those in the Ad-GFP group (P<0.01); Meanwhile, MitoTracker® staining showed that the mitochondrial fission was increased and the mitochondrial size frequency distribution shifted left in the Ad-ROCK1 group. After exposed to fasudil. the OCR and EACR of C2C12 myoblasts in the Ad-ROCKIF group were significantly decreased versus the Ad-ROCK1 group, and the basal respiration and maximal respiration were significantly increased (P<0.05). Western blotting analysis showed that p-Drpl/Drpl ratio, and the expressions of ROCK1, MuRFl and Atroginl in Ad-ROCKIF group were significantly reduced compared with Ad-ROCKl group (P<0.05). Conclusion Fasudil, an inhibitor of ROCK1, can block the abnormal cell respiration of C2C12 myoblasts caused by overexpressed ROCK 1 in vitro, and can reduce the activity of mitochondrial kinetic protein and the expression of muscle atrophy-related proteins.
ABSTRACT
MicroRNA (miRNA) is involved in the regulation of many genes at the post-transcriptional level and plays an important role in many physiological and pathological processes. More and more evidence suggests that muscle atrophy diseases are related to the regulation of miRNA , which indicting that miRNA may have a great potential to become biomarkers and drug targets for the treatment and diagnosis of the disease. This paper outlined the progress of miRNA in muscle atrophy, hoping to provide a theoretical basis for the prevention and treatment of muscle diseases.