Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 46, Issue 8, Pages 1109-1118Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.01.014
Keywords
Intracellular antioxidant enzymes; Base excision repair (BER); Fibroblasts; Snell dwarf mice; Stress resistance; Lifespan; Serum deprivation; Paraquat; Hydrogen peroxide
Funding
- Ontario Graduate Scholarship
- Canada Graduate Scholarship
- Natural Sciences and Engineering Research Council
- Canada Foundation for Innovation
- NIA [AG023122, AG024824, AG000114]
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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 O-2; 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% O-2, 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. (C) 2009 Elsevier Inc. All rights reserved.
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