Proteomic analysis of tumor necrosis factor-alpha (TNF-α)-induced L6 myotube secretome reveals novel TNF-α-dependent myokines in diabetic skeletal muscle

Jong Hyuk Yoon, Parkyong Song, Jin Hyeok Jang, Dae Kyum Kim, Sunkyu Choi, Jaeyoon Kim, Jaewang Ghim, Dayea Kim, Sehoon Park, Hyeongji Lee, Dongoh Kwak, Kyungmoo Yea, Daehee Hwang, Pann Ghill Suh, Sung Ho Ryu

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32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5315-5325
Number of pages11
JournalJournal of Proteome Research
Volume10
Issue number12
DOIs
Publication statusPublished - 2 Dec 2011
Externally publishedYes

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Keywords

  • chronic inflammation
  • diabetes
  • insulin resistance
  • proteomics
  • secretory proteins
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Yoon, J. H., Song, P., Jang, J. H., Kim, D. K., Choi, S., Kim, J., Ghim, J., Kim, D., Park, S., Lee, H., Kwak, D., Yea, K., Hwang, D., Suh, P. G., & Ryu, S. H. (2011). Proteomic analysis of tumor necrosis factor-alpha (TNF-α)-induced L6 myotube secretome reveals novel TNF-α-dependent myokines in diabetic skeletal muscle. Journal of Proteome Research, 10(12), 5315-5325. https://doi.org/10.1021/pr200573b