Nox 2 stimulates muscle differentiation via NF-κB/iNOS pathway

Yu Ji Piao, Yong Hak Seo, Feng Hong, Jin Hwan Kim, Young Joo Kim, Myung Ho Kang, Bum Shik Kim, Sangmee Ahn Jo, Inho Jo, Dae Myung Jue, Insug Kang, Joohun Ha, Sung Soo Kim

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


The NF-κB/iNOS pathway stimulates muscle differentiation downstream of the PI 3-kinase/p38 MAPK pathway and diverse antioxidants block muscle differentiation. Therefore, we here investigated whether Nox 2 links those two myogenic pathways in H9c2 and C2C12 myoblasts. Compared with the proliferation stage, ROS generation was enhanced from the early stage of differentiation and gradually increased as differentiation progressed. Antioxidants suppressed the activated NF-κB/iNOS pathway during muscle differentiation. Nox 2 activity was also increased during muscle differentiation. Treatment with DPI and apocynin, two inhibitors of NADPH oxidase, and suppression of Nox 2 expression using siRNA, but not Nox 1, inhibited NADPH oxidase activity, muscle differentiation, and the NF-κB/iNOS pathway. Inhibition of PI 3-kinase and p38 MAPK suppressed the Nox 2/NF-κB/iNOS pathway. Nitric oxide restored muscle differentiation blocked by treatment with antioxidants or suppression of the Nox 2/NF-κB/iNOS pathway. In conclusion, Nox 2 stimulates muscle differentiation downstream of the PI 3-kinase/p38 MAPK pathway by activating the NF-κB/iNOS pathway via ROS generation.

Original languageEnglish
Pages (from-to)989-1001
Number of pages13
JournalFree Radical Biology and Medicine
Issue number8
StatePublished - 15 Apr 2005

Bibliographical note

Funding Information:
We thank Drs. J.F. Peyron, M. Kasuga, R.J. Davis, Y.S. Bae, and J. Downward for providing us with various plasmids. We also thank Dr. H. Jo at Emory University for helpful discussion. This work was supported by grants from the Korea Science & Engineering Foundation (No. R13-2002-020-01001-0) and the Ministry of Public Health and Welfare (02-PJ1-PG10-20908-0005), Republic of Korea.


  • Free radicals
  • Muscle differentiation
  • NF-κB
  • Nitric oxide
  • Nox 2
  • PI 3-kinase
  • Reactive oxygen species (ROS)
  • iNOS
  • p38 MAPK


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