Oxidative modification and aggregation of creatine kinase from aged mouse skeletal muscle.

Jonathan E. Nuss, James K. Amaning, C. Eric Bailey, James H. DeFord, Vincent L. Dimayuga, Jeffrey P. Rabek, John Papaconstantinou

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Creatine kinase catalyzes the reversible transfer of the gamma phosphate from ATP to creatine forming the high energy compound creatine phosphate. Muscle creatine kinase (CKm) activity maintains energetic homeostasis as variations in energy requirements dictate that ATP be readily available. Recent studies suggest that CKm activity is altered during aging. Proteomic analyses have shown that CKm is 3-nitrotyrosine (3-NT) modified and carbonylated in aged rodent skeletal muscle. However, it remains unknown if these modifications affect its structure and activity. To address this we characterized oxidatively modified CKm from the quadriceps of young, middle-aged, and aged mice. Our data indicate that 3-NT modified and carbonylated CKm are found predominantly in aged muscle and that it exists in high molecular weight oligomers and insoluble protein aggregates. CKm from middle-aged and aged mouse quadriceps also exhibits structural instability that may account for its reduction in function. These structural and functional changes correlate with the differential protein modifications. Interestingly, the majority of the age-related changes in enzyme activity and protein stability occurred by middle age. Our studies indicate that the age-associated oxidative and nitrative modification of CKm results in a decrease in its activity and may cause structural changes that promote oligomerization and aggregation.

Original languageEnglish (US)
Pages (from-to)557-572
Number of pages16
JournalAging
Volume1
Issue number6
StatePublished - Jun 2009
Externally publishedYes

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Creatine Kinase
Skeletal Muscle
Adenosine Triphosphate
MM Form Creatine Kinase
Enzyme Stability
Phosphocreatine
Creatine
Protein Stability
Proteomics
Rodentia
Homeostasis
Molecular Weight
Phosphates
Muscles
Proteins
3-nitrotyrosine
Protein Aggregates

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

Nuss, J. E., Amaning, J. K., Bailey, C. E., DeFord, J. H., Dimayuga, V. L., Rabek, J. P., & Papaconstantinou, J. (2009). Oxidative modification and aggregation of creatine kinase from aged mouse skeletal muscle. Aging, 1(6), 557-572.

Oxidative modification and aggregation of creatine kinase from aged mouse skeletal muscle. / Nuss, Jonathan E.; Amaning, James K.; Bailey, C. Eric; DeFord, James H.; Dimayuga, Vincent L.; Rabek, Jeffrey P.; Papaconstantinou, John.

In: Aging, Vol. 1, No. 6, 06.2009, p. 557-572.

Research output: Contribution to journalArticle

Nuss, JE, Amaning, JK, Bailey, CE, DeFord, JH, Dimayuga, VL, Rabek, JP & Papaconstantinou, J 2009, 'Oxidative modification and aggregation of creatine kinase from aged mouse skeletal muscle.', Aging, vol. 1, no. 6, pp. 557-572.
Nuss JE, Amaning JK, Bailey CE, DeFord JH, Dimayuga VL, Rabek JP et al. Oxidative modification and aggregation of creatine kinase from aged mouse skeletal muscle. Aging. 2009 Jun;1(6):557-572.
Nuss, Jonathan E. ; Amaning, James K. ; Bailey, C. Eric ; DeFord, James H. ; Dimayuga, Vincent L. ; Rabek, Jeffrey P. ; Papaconstantinou, John. / Oxidative modification and aggregation of creatine kinase from aged mouse skeletal muscle. In: Aging. 2009 ; Vol. 1, No. 6. pp. 557-572.
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