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    Ishemia-Reperfusion Enhances Gapdh Nitration In Aging Skeletal Muscle

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    IshemiaReperfusion.pdf (2.396Mb)
    Date
    2011-10
    Author
    Bailey, C. E.
    Hammers, D. W.
    DeFord, J. H.
    Dimayuga, V. L.
    Amaning, J. K.
    Farrar, R.
    Papaconstantinou, J.
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    Abstract
    Aging and skeletal muscle ischemia/reperfusion (I/R) injury leads to decreased contractile force generation that increases severely with age. Our studies show that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein expression is significantly decreased at 3 and 5 days reperfusion in the young mouse muscle and at 1, 3, 5, and 7 days in the aged muscle. Using PCR, we have shown that GAPDH mRNA levels in young and old muscle increase at 5 days reperfusion compared to control, suggesting that the protein deficit is not transcriptional. Furthermore, while total tyrosine nitration did not increase in the young muscle, GAPDH nitration increased significantly at 1 and 3 days reperfusion. In contrast, total tyrosine nitration in aged muscle increased significantly at 1, 3, and 5 days of reperfusion, with increases in GAPDH nitration at the same time points. We conclude that GAPDH protein levels decrease following I/R, that this is not transcriptionally mediated, that the aged muscle experiences greater oxidative stress, protein modification and GAPDH degradation, possibly contributing to decreased muscle function. We propose that tyrosine nitration enhances GAPDH degradation following I/R and that the persistent decrease of GAPDH in aged muscle is due to the prolonged increase in oxidative modification in this age group.
    Department
    Biochemistry
    Subject
    skeletal muscle
    gapdh
    nitration
    ischemia/reperfusion
    aging
    chaperone-mediated autophagy
    nitric-oxide synthase
    glyceraldehyde-3-phosphate dehydrogenase
    oxidative stress
    cell-death
    3-nitropropionic acid
    ischemia-reperfusion
    translation arrest
    protein-synthesis
    s-nitrosylation
    cell biology
    URI
    http://hdl.handle.net/2152/29295
    Citation
    C. Eric Bailey, David W. Hammers, James H. DeFord, Vincent L. Dimayuga, James K. Amaning, Roger Farrar, and John Papaconstantinou. AGING, Vol. 3 No 10, pp. 1003-1017; (Oct., 2011)
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    • facebook
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    • CONTACT US
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