TY - JOUR
T1 - Glutathione-peroxidase-1 null muscle progenitor cells are globally defective
AU - Lee, Sukkyoo
AU - Shin, H. Stella
AU - Shireman, Paula K.
AU - Vasilaki, Aphrodite
AU - Van Remmen, Holly
AU - Csete, Marie E.
PY - 2006/10/1
Y1 - 2006/10/1
N2 - 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.
AB - 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.
KW - Glutathione peroxidase-1
KW - Myoblast
KW - Myotube
KW - Peroxide
KW - Reactive oxygen species
KW - Skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=33748290201&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748290201&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2006.07.005
DO - 10.1016/j.freeradbiomed.2006.07.005
M3 - Article
C2 - 16962942
AN - SCOPUS:33748290201
VL - 41
SP - 1174
EP - 1184
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 7
ER -