Elevated protein carbonylation and oxidative stress do not affect protein structure and function in the long-living naked-mole rat: A proteomic approach

Eric M. De Waal, Hanyu Liang, Anson Pierce, Ryan T. Hamilton, Rochelle Buffenstein, Asish R. Chaudhuri

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    The 'oxidative stress theory of aging' predicts that aging is primarily regulated by progressive accumulation of oxidized macromolecules that cause deleterious effects to cellular homeostasis and induces a decline in physiological function. However, our reports on the detection of higher level of oxidized protein carbonyls in the soluble cellular fractions of long-living rodent naked-mole rats (NMRs, lifespan ~30. yrs) compared to short-lived mice (lifespan ~3.5. yrs) apparently contradicts a key tenet of the oxidative theory. As oxidation often inactivates enzyme function and induces higher-order soluble oligomers, we performed a comprehensive study to measure global protein carbonyl level in different tissues of age-matched NMRs and mice to determine if the traditional concept of oxidation mediated impairment of function and induction of higher-order structures of proteins are upheld in the NMRs. We made three intriguing observations with NMRs proteins: (1) protein carbonyl is significantly elevated across different tissues despite of its exceptional longevity, (2) enzyme function is restored despite of experiencing higher level of protein carbonylation, and (3) enzymes show lesser sensitivity to form higher-order non-reducible oligomers compared to short-living mouse proteins in response to oxidative stress. These observations were made based on the global analysis of protein carbonyl and identification of two heavily carbonylated proteins in the kidney, triosephosphate isomerase (TPI) and cytosolic peroxiredoxin (Prdx1). These un-expected intriguing observations thus strongly suggest that oxidative modification may not be the only criteria for impairment of protein and enzyme function; cellular environment is likely be the critical determining factor in this process and may be the underlying mechanism for exceptional longevity of NMR.

    Original languageEnglish (US)
    Pages (from-to)815-819
    Number of pages5
    JournalBiochemical and Biophysical Research Communications
    Volume434
    Issue number4
    DOIs
    StatePublished - May 17 2013

    Fingerprint

    Mole Rats
    Protein Carbonylation
    Carbonylation
    Oxidative stress
    Proteomics
    Rats
    Oxidative Stress
    Proteins
    Nuclear magnetic resonance
    Enzymes
    Oligomers
    Triose-Phosphate Isomerase
    Aging of materials
    Peroxiredoxins
    Tissue
    Oxidation
    Macromolecules
    Rodentia
    Homeostasis

    Keywords

    • Naked-mole rat
    • Oxidative stress
    • Peroxiredoxin 1
    • Protein carbonylation
    • Triosephosphate isomerase

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology
    • Molecular Biology

    Cite this

    Elevated protein carbonylation and oxidative stress do not affect protein structure and function in the long-living naked-mole rat : A proteomic approach. / De Waal, Eric M.; Liang, Hanyu; Pierce, Anson; Hamilton, Ryan T.; Buffenstein, Rochelle; Chaudhuri, Asish R.

    In: Biochemical and Biophysical Research Communications, Vol. 434, No. 4, 17.05.2013, p. 815-819.

    Research output: Contribution to journalArticle

    De Waal, Eric M. ; Liang, Hanyu ; Pierce, Anson ; Hamilton, Ryan T. ; Buffenstein, Rochelle ; Chaudhuri, Asish R. / Elevated protein carbonylation and oxidative stress do not affect protein structure and function in the long-living naked-mole rat : A proteomic approach. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 434, No. 4. pp. 815-819.
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