Indoxyl sulfate induces myotube atrophy by ROS-ERK and JNK-MAFbx cascades.
Chem Biol Interact
; 304: 43-51, 2019 May 01.
Article
em En
| MEDLINE
| ID: mdl-30849338
ABSTRACT
Accumulations of uremic toxins has been widely recognized as the major trigger of skeletal muscle loss in chronic kidney disease (CKD), which is defined as uremic sarcopenia. Current study was aimed to examine the effects of representative uremic toxin, indoxyl sulfate (IS), on C2C12 myotubes. The incubation of IS (from 0.1â¯mM to 1.2â¯mM) exerted the reduction in myotube diameter without cell survival impairment. Elevated oxidative stress and mitogen-activated protein kinase (MAPKs) phosphorylation were observed after IS stimulation for 1 and 24â¯h. After N-acetylcysteine (NAC) treatment as antioxidants, the recovery in IS-induced decrease myotube diameter and ERK phosphorylation was observed. This findings were implicit the transduction of p-ERK in IS-induced ROS toxicity. Moreover, the increase of LC3ß was found closely with IS treatment in C2C12 myotubes. The reverse effect of NAC on LC3ß expression revealed the ROS-responsibility in autophagy regulation of CKD myopathy. The evaluation of IS-treated proteasome system showed increased phospho-myosin light chain, along with the upregulation of muscle atrophy F-box (MAFbx) mRNA and protein. This alteration in MAFbx was also identified in nephrectomy-induced CKD model. Besides, the inhibition of p-JNK was capable to attenuate IS-induced upward change in MAFbx protein expression. These findings indicated that IS-mediated myotube atrophy may manipulate through ROS-ERK axis and JNK-MAFbx regulation in C2C12â¯cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Atrofia Muscular
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Espécies Reativas de Oxigênio
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Proteínas Ligases SKP Culina F-Box
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MAP Quinases Reguladas por Sinal Extracelular
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Proteínas Quinases JNK Ativadas por Mitógeno
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Indicã
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Proteínas Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Chem Biol Interact
Ano de publicação:
2019
Tipo de documento:
Article