Sod2 overexpression preserves myoblast mitochondrial mass and function, but not muscle mass with aging

Sukkyoo Lee, Holly Van Remmen, Marie Csete

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Mice lacking superoxide dismutase-2 (SOD2 or MnSOD) die during embryonic or early neonatal development, with diffuse superoxide-induced mitochondrial damage. Although stem and progenitor cells are exquisitely sensitive to oxidant stress, they have not been well studied in MnSOD2-manipulated mouse models. Patterns of proliferation and differentiation of cultured myoblasts (muscle progenitor cells), PI3-Akt signaling during differentiation, and the maintenance of mitochondrial mass with aging using myoblasts from young (3-4 week old) and aged (27-29 months old) MnSOD2-overexpressing (Sod2-Tg) and heterozygote (Sod2+/-) mice were characterized by us. Overexpression of MnSOD2 in myoblasts had a protective effect on mitochondrial DNA abundance and some aspects of mitochondrial function with aging, and preservation of differentiation potential. Sod2 deficiency resulted in defective signaling in the PI3-Akt pathway, specifically impaired phosphorylation of Akt at Ser473 and Thr308 in young myoblasts, and decreased differentiation potential. Compared with young myoblasts, aged myoblast Akt was constitutively phosphorylated, unresponsive to mitogen signaling, and indifferent to MnSOD2 levels. These data suggest that specific sites in the PI3K-Akt pathway are more sensitive to increased superoxide levels than to the increased hydrogen peroxide levels generated in Sod2-transgenic myoblasts. In wild-type myoblasts, aging was associated with significant loss of mitochondrial DNA relative to chromosomal DNA, but MnSOD2 overexpression was associated with maintained myoblast mitochondrial DNA with aging.

Original languageEnglish (US)
Pages (from-to)296-310
Number of pages15
JournalAging Cell
Volume8
Issue number3
DOIs
StatePublished - Jun 5 2009

Keywords

  • Hydrogen peroxide;
  • Mitochondria
  • Muscle aging
  • Myoblast
  • PI3 kinase-Akt signaling
  • Superoxide

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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