TY - JOUR
T1 - Regulation of proliferation of skeletal muscle precursor cells by NADPH oxidase
AU - Mofarrahi, Mahroo
AU - Brandes, Ralf P.
AU - Gorlach, Agnes
AU - Hanze, Joerg
AU - Terada, Lance S.
AU - Quinn, Mark T.
AU - Mayaki, Dominique
AU - Petrof, Basil
AU - Hussain, Sabah N A
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
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U2 - 10.1089/ars.2007.1792
DO - 10.1089/ars.2007.1792
M3 - Article
C2 - 18092937
AN - SCOPUS:38349078194
SN - 1523-0864
VL - 10
SP - 559
EP - 574
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 3
ER -