title: Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration.
abstract: Mammalian skeletal muscle can remodel, repair, and regenerate itself by mobilizing satellite cells, a resident population of myogenic progenitor cells. Muscle injury and subsequent activation of myogenic progenitor cells is associated with oxidative stress. Cytoglobin is a hemoprotein expressed in response to oxidative stress in a variety of tissues, including striated muscle. In this study, we demonstrate that cytoglobin is up-regulated in activated myogenic progenitor cells, where it localizes to the nucleus and contributes to cell viability. siRNA-mediated depletion of cytoglobin from C2C12 myoblasts increased levels of reactive oxygen species and apoptotic cell death both at baseline and in response to stress stimuli. Conversely, overexpression of cytoglobin reduced reactive oxygen species levels, caspase activity, and cell death. Mice in which cytoglobin was knocked out specifically in skeletal muscle were generated to examine the role of cytoglobin in vivo. Myogenic progenitor cells isolated from these mice were severely deficient in their ability to form myotubes as compared with myogenic progenitor cells from wild-type littermates. Consistent with this finding, the capacity for muscle regeneration was severely impaired in mice deficient for skeletal-muscle cytoglobin. Collectively, these data demonstrate that cytoglobin serves an important role in muscle repair and regeneration.
authors.affiliation: Departments of Internal Medicine, Molecular Biology, and Pathology, the Donald W. Reynolds Cardiovascular Clinical Research Center, and the Heart Failure, Ventricular Assist Device and Heart Transplant Program, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Sarvjeet
authors.initials: S
authors.lastname: Singh
authors.forename: Diana C
authors.initials: DC
authors.lastname: Canseco
authors.forename: Shilpa M
authors.initials: SM
authors.lastname: Manda
authors.forename: John M
authors.initials: JM
authors.lastname: Shelton
authors.forename: Rajendra R
authors.initials: RR
authors.lastname: Chirumamilla
authors.forename: Sean C
authors.initials: SC
authors.lastname: Goetsch
authors.forename: Qiu
authors.initials: Q
authors.lastname: Ye
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gerard
authors.forename: Jay W
authors.initials: JW
authors.lastname: Schneider
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Rothermel
authors.forename: Pradeep P A
authors.initials: PP
authors.lastname: Mammen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D000078842:Cytoglobin; D005786:Gene Expression Regulation; D005914:Globins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors
chemical_list: C000627267:Cygb protein, mouse; D000078842:Cytoglobin; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D005914:Globins
keywords: myocyte differentiation/proliferation; myogenesis; nuclear protein; redox signaling