Mechanisms of stress resistance in Snell dwarf mouse fibroblasts: Enhanced antioxidant and DNA base excision repair capacity, but no differences in mitochondrial metabolism

Melissa M. Page, Adam B. Salmon, Scott F. Leiser, Ellen L. Robb, Melanie F. Brown, Richard A. Miller, Jeffrey A. Stuart

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Dermal fibroblasts from long-lived Snell dwarf mice can withstand a variety of oxidative and non-oxidative stressors compared to normal littermate controls. Here, we report differences in the levels and activities of intracellular antioxidant and DNA repair enzymes between normal and Snell dwarf mice fibroblasts cultured under a variety of conditions, including: 3% and 20% ambient O2; the presence and absence of serum; and the addition of an exogenous oxidative stress. The only significant difference between normal and dwarf cells cultured in complete medium, at 20% O2, was an approximately 40% elevation of glutathione peroxidase (GPx) activity in the mutant cells. Serum deprivation elicited increases in GPx in both genotypes, but these activities remained higher in dwarf mouse cells. Dwarf mouse cells deprived of serum and challenged with exposure to paraquat or hydrogen peroxide showed a generally greater upregulation of catalase and DNA base excision repair enzymes. As these toxins can interact with mitochondria to increase mitochondrial ROS production, we explored whether there were differences in mitochondrial metabolism between normal and dwarf mouse cells. However, neither mitochondrial content nor the apparent mitochondrial membrane potential differed between genotypes. Overall, the results suggest that superior hydrogen peroxide metabolism and a marginally greater DNA base excision repair capacity contribute to the stress resistance phenotype of Snell dwarf mouse fibroblasts.

Original languageEnglish (US)
Pages (from-to)1109-1118
Number of pages10
JournalFree Radical Biology and Medicine
Volume46
Issue number8
DOIs
Publication statusPublished - Apr 15 2009

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Keywords

  • Base excision repair (BER)
  • Fibroblasts
  • Hydrogen peroxide
  • Intracellular antioxidant enzymes
  • Lifespan
  • Paraquat
  • Serum deprivation
  • Snell dwarf mice
  • Stress resistance

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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