Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Sarvjeet Singh, Diana C. Canseco, Shilpa M. Manda, John M. Shelton, Rajendra R. Chirumamilla, Sean C. Goetsch, Qiu Ye, Robert D. Gerard, Jay W. Schneider, James A. Richardson, Beverly A. Rothermel, Pradeep P A Mammen

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number1
DOIs
StatePublished - 2014

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Regeneration
Cell Survival
Stem Cells
Muscles
Skeletal Muscle
Reactive Oxygen Species
Oxidative Stress
Cell Death
Striated Muscle
cytoglobin
Myoblasts
Skeletal Muscle Fibers
Caspases
Small Interfering RNA
Wounds and Injuries
Population

Keywords

  • Myocyte differentiation/proliferation
  • Myogenesis
  • Nuclear protein
  • Redox signaling

ASJC Scopus subject areas

  • General

Cite this

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration. / Singh, Sarvjeet; Canseco, Diana C.; Manda, Shilpa M.; Shelton, John M.; Chirumamilla, Rajendra R.; Goetsch, Sean C.; Ye, Qiu; Gerard, Robert D.; Schneider, Jay W.; Richardson, James A.; Rothermel, Beverly A.; Mammen, Pradeep P A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 1, 2014.

Research output: Contribution to journalArticle

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