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

25 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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