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

Mark A. Madsen, Ching Chyuan Hsieh, William H. Boylston, Kevin Flurkey, David Harrison, John Papaconstantinou

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 (Pit1dw/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 Ser63 in dwarf mice after 3-NPA treatment, despite a robust phosphorylation of Ser63 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.

Original languageEnglish (US)
Pages (from-to)998-1005
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number4
DOIs
StatePublished - Jun 11 2004

Fingerprint

Oxidative stress
Oxidative Stress
Phosphorylation
Mitogen-Activated Protein Kinase Kinases
Phosphotransferases
Genes
Aging of materials
MAP Kinase Kinase Kinases
Chemical activation
Mutation
Life Expectancy

Keywords

  • 3-NPA
  • AP-1
  • Longevity
  • MAP kinase
  • Oxidative stress
  • Snell dwarf

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Altered oxidative stress response of the long-lived Snell dwarf mouse. / Madsen, Mark A.; Hsieh, Ching Chyuan; Boylston, William H.; Flurkey, Kevin; Harrison, David; Papaconstantinou, John.

In: Biochemical and Biophysical Research Communications, Vol. 318, No. 4, 11.06.2004, p. 998-1005.

Research output: Contribution to journalArticle

Madsen, Mark A. ; Hsieh, Ching Chyuan ; Boylston, William H. ; Flurkey, Kevin ; Harrison, David ; Papaconstantinou, John. / Altered oxidative stress response of the long-lived Snell dwarf mouse. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 318, No. 4. pp. 998-1005.
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