Regulation of proliferation of skeletal muscle precursor cells by NADPH oxidase

Mahroo Mofarrahi, Ralf P. Brandes, Agnes Gorlach, Joerg Hanze, Lance S. Terada, Mark T. Quinn, Dominique Mayaki, Basil Petrof, Sabah N A Hussain

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Skeletal muscle precursor cells are adult stem cells located among muscle fibers. Proliferation, migration, and subsequent differentiation of these cells are critical steps in the repair of muscle injury. We document in this study the roles and mechanisms through which the NAPDH oxidase complex regulates muscle precursor cell proliferation. The NADPH oxidase subunits Nox2, Nox4, p22 phox, p47phox, and p67phox were detected in primary human and murine skeletal muscle precursor cells. In human muscle precursor cells, NADPH oxidase-fusion proteins were localized in the cytosolic and membrane compartments of the cell, except for p47phox, which was detected in the nucleus. In proliferating subconfluent precursor cells, both Nox2 and Nox4 contributed to O2- production. However, Nox4 expression was significantly attenuated in differentiated myotubes. Proliferation of precursor cells was significantly reduced by antioxidants (N-acetylcysteine and apocynin), inhibition of p22phox expression by using siRNA oligonucleotides, and reduction of Nox4 and p47phox activities with dominant-negative vectors and siRNA oligonucleotides resulted in attenuation of activities of the Erk1/2, PI-3 kinase/AKT and NFκB pathways and significant reduction in cyclin D1 levels. We conclude that NADPH oxidase is expressed in skeletal muscle precursor cells and that its activity plays an important role in promoting proliferation of these cells.

Original languageEnglish (US)
Pages (from-to)559-574
Number of pages16
JournalAntioxidants and Redox Signaling
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Mofarrahi, M., Brandes, R. P., Gorlach, A., Hanze, J., Terada, L. S., Quinn, M. T., Mayaki, D., Petrof, B., & Hussain, S. N. A. (2008). Regulation of proliferation of skeletal muscle precursor cells by NADPH oxidase. Antioxidants and Redox Signaling, 10(3), 559-574. https://doi.org/10.1089/ars.2007.1792