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Protein modification in aging

  • E. R. Stadtman
  • P. E. Starke-Reed
  • C. N. Oliver
  • J. M. Carney
  • R. A. Floyd
Part of the EXS book series (EXS, volume 62)

Summary

During aging a number of enzymes accumulate as catalytically inactive or less active forms. The age-related changes in catalytic activity are due in part to reactions of the protein with “active” oxygen species such as ozone, singlet oxygen, or with oxygen free radicals as are produced during exposure to ionizing radiation or to metal ion catalyzed oxidation (MCO) systems. The levels of oxidized proteins in cultured human fibroblasts from individuals of various ages and in liver and brain extracts of rats of different ages increase progressively with age, and in old rats can represent 30–50% of the total cellular protein. The age-related increase in oxidized protein in rat liver and brain tissue is accompanied by a loss of glutamine synthetase (GS) and glucose-6-P dehydrogenase (G-6-PDH) activities, and to a decrease in the level of cytosolic neutral protease activity which is responsible for the degradation of oxidized (denatured) protein. Of particular significance are the results of experiments showing that similar age-related changes occur in the gerbil brain and that these changes are accompanied by a loss of short-term memory as measured by the radial arm maze technique. Chronic treatment (intraperitoneal injections) of old animals with the free radical spin-trap reagent, N-tert-butyl-α-phenylnitrone (PBN) resulted in normalization of the several biochemical parameters to those characteristic of the young animals; coincidentally, the short-term memory index was restored to the young animal values. These results provide the first evidence that there is likely a linkage between the age-dependent accumulation of oxidized enzymes and the loss of physiological function.

Keywords

Glutamine Synthetase Total Cellular Protein Metal Binding Site Gerbil Brain Cysteinyl Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag Basel/Switzerland 1992

Authors and Affiliations

  • E. R. Stadtman
    • 1
  • P. E. Starke-Reed
    • 2
  • C. N. Oliver
    • 3
  • J. M. Carney
    • 4
  • R. A. Floyd
    • 5
  1. 1.Laboratory of Biochemistry, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Geriatrics Program, National Institute on AgingNational Institutes of HealthBethesdaUSA
  3. 3.Merck Sharp & Dohme Research LaboratoriesPennsylvaniaUSA
  4. 4.Department of Pharmacology, Chandler Medical CenterUniversity of KentuckyLexingtonUSA
  5. 5.Department of Molecular ToxicologyOklahoma Medical Research FoundationOklahoma CityUSA

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