Apoptosis

, Volume 13, Issue 6, pp 822–832

Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice

  • Melissa Braga
  • Amiya P. Sinha Hikim
  • Sanjit Datta
  • Monica G. Ferrini
  • Danielle Brown
  • Ekaterina L. Kovacheva
  • Nestor F. Gonzalez-Cadavid
  • Indrani Sinha-Hikim
Original Paper

DOI: 10.1007/s10495-008-0216-7

Cite this article as:
Braga, M., Sinha Hikim, A.P., Datta, S. et al. Apoptosis (2008) 13: 822. doi:10.1007/s10495-008-0216-7

Abstract

Apoptosis has been implicated as a mechanism of loss of muscle cells in normal aging and plays an important role in age-related sarcopenia. To test the hypothesis that caspase 2 and c-Jun NH2-terminal kinase (JNK)-mediated intrinsic pathway signaling contribute to skeletal muscle cell apoptosis in aging, we compared activation of caspase 2 and JNK and the in vivo expression of 4-hydroxynonenal protein adducts (4-HNE), inducible nitric oxide synthase (iNOS), glucose-6-phosphate dehydrogenase (G6PDH), B-cell lymphoma-2 (BCL-2), BAX, and phospho-BCL-2 in gastrocnemius muscles of young (5 months old) and old (25 months old) mice. A distinct age-related increase in 4-HNE and iNOS expression was readily detected in mice. Increased oxidative stress and iNOS induction were further accompanied by a decrease in G6PDH expression, activation of caspase 2 and JNK, and inactivation of BCL-2 through phosphorylation at serine 70, and caspase 9 activation. Regression analysis further revealed that increased muscle cell death in aging was significantly correlated with changes in the levels of these molecules. Taken together, our data indicate that caspase 2 and JNK-mediated intrinsic pathway signaling is one of the mechanisms involved in age-related increase in muscle cell apoptosis.

Keywords

Oxidative stressCaspase 2JNKBCL-2 phosphorylationMuscle cell apoptosisAgingMice

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Melissa Braga
    • 1
  • Amiya P. Sinha Hikim
    • 2
  • Sanjit Datta
    • 2
    • 3
  • Monica G. Ferrini
    • 1
  • Danielle Brown
    • 1
  • Ekaterina L. Kovacheva
    • 1
  • Nestor F. Gonzalez-Cadavid
    • 1
    • 2
    • 3
  • Indrani Sinha-Hikim
    • 1
  1. 1.Division of Endocrinology, Metabolism, and Molecular Medicine (I.S.-H;M.B; R.S)Charles R. Drew UniversityLos AngelesUSA
  2. 2.Division of Endocrinology, Harbor-UCLA Medical CenterDavid Geffen School of Medicine at UCLA and Los Angeles Biomedical Research InstituteTorranceUSA
  3. 3.Los Angeles Biomedical Research InstituteTorranceUSA