Proteomic analysis of tumor necrosis factor-alpha (TNF-α)-induced L6 myotube secretome reveals novel TNF-α-dependent myokines in diabetic skeletal muscle.
J Proteome Res
; 10(12): 5315-25, 2011 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-22023146
ABSTRACT
There is a strong possibility that skeletal muscle can respond to irregular metabolic states by secreting specific cytokines. Obesity-related chronic inflammation, mediated by pro-inflammatory cytokines, is believed to be one of the causes of insulin resistance that results in type 2 diabetes. Here, we attempted to identify and characterize the members of the skeletal muscle secretome in response to tumor necrosis factor-alpha (TNF-α)-induced insulin resistance. To conduct this study, we comparatively analyzed the media levels of proteins released from L6 skeletal muscle cells. We found 28 TNF-α modulated secretory proteins by using separate filtering methods:
Gene Ontology, SignalP, and SecretomeP, as well as the normalized Spectral Index for label-free quantification. Ten of these secretory proteins were increased and 18 secretory proteins were decreased by TNF-α treatment. Using microarray analysis of Zuker diabetic rat skeletal muscle combined with bioinformatics and Q-PCR, we found a correlation between TNF-α-mediated insulin resistance and type 2 diabetes. This novel approach combining analysis of the conditioned secretome and transcriptome has identified several previously unknown, TNF-α-dependent secretory proteins, which establish a foothold for research on the different causes of insulin resistance and their relationships with each other.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
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Fator de Necrose Tumoral alfa
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Músculo Esquelético
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Fibras Musculares Esqueléticas
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Proteômica
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Proteínas Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article