Altered oxidative stress response of the long-lived Snell dwarf mouse

• Published in: Biochemical and biophysical research communications 2004-06, Vol.318 (4), p.998-1005
• Main Authors: Madsen, Mark A, Hsieh, Ching-Chyuan, Boylston, William H, Flurkey, Kevin, Harrison, David, Papaconstantinou, John
• Format: Article
• Language: English
• Subjects: 3-NPA; Animals; AP-1; Cell Nucleus - metabolism; Cytosol - enzymology; Dwarfism, Pituitary - enzymology; Dwarfism, Pituitary - genetics; Dwarfism, Pituitary - metabolism; Female; Liver - enzymology; Longevity; Longevity - genetics; Longevity - physiology; MAP kinase; MAP Kinase Signaling System - physiology; Mice; Mice, Inbred Strains; Mitogen-Activated Protein Kinases - metabolism; Nitro Compounds; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Oxidative Stress - physiology; Phosphorylation; Propionates - pharmacology; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Snell dwarf
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.04.126

Several single gene mutations in mice that increase the murine life span have been identified, including the Pit-1 mutation which results in the Snell dwarf ( Pit1 dw/dw ), however, the biological mechanism of this life-span extension is still unclear. Based on studies that show oxidative stress plays an important role in the aging process, we hypothesized that the increased longevity seen in Snell dwarf mice may result from a resistance to oxidative stress. We report that Snell dwarf mice respond to oxidative stress induced by 3-NPA differently than their wild type littermates. This altered response results in diminished activation of the MEK–ERK kinase cascade and virtually no phosphorylation of c-Jun at Ser 63 in dwarf mice after 3-NPA treatment, despite a robust phosphorylation of Ser 63 in wild type mice. We propose that this altered management of oxidative stress in dwarf mice is partially responsible for the increased longevity in Snell dwarf mice.