Glutathione-peroxidase-1 null muscle progenitor cells are globally defective.
Mice lacking glutathione peroxidase-1 (Gpx1) have decreased resistance to systemically administered oxidants as well as infections, and sustain increased damage after ischemia-reperfusion injuries. However, stem or progenitor cell function in these animals has not been studied. We characterized patterns of proliferation, apoptosis, and differentiation of primary muscle progenitor cells (myoblasts) from Gpx1(-/-) mice. Myoblasts are the transit amplifying compartment of skeletal muscle. All aspects of myoblast biology are negatively affected by deletion of Gpx1. In particular, passaged, proliferating Gpx1(-/-) myoblasts, when induced to differentiate into fused multinucleated myotubes, show significant impairment, and form only a few immature myotubes. This defect occurs despite increased expression of the core regulators of muscle differentiation, the myogenic basic helix-loop-helix (bHLH) transcription factors, in the Gpx1(-/-) myoblasts. Furthermore, Gpx1(-/-) myoblasts exhibited decreased proliferation and increased apoptosis compared to wild-type cells. In vivo, muscle fiber areas are decreased in Gpx1(-/-) vs wild-type mice. These data suggest that Gpx1 is important for adult muscle progenitor cell function at many levels, is necessary for integrity of muscle differentiation, and that quiescent resident stem cell populations may be particularly vulnerable to peroxide-mediated damage.
Lee
Sukkyoo
S
Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30333, USA.
Shin
H Stella
HS
Shireman
Paula K
PK
Vasilaki
Aphrodite
A
Van Remmen
Holly
H
Csete
Marie E
ME
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000166:cytology*; D032448:Myoblasts, Skeletal / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D000094765:Glutathione Peroxidase GPX1
D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse