The importance of antioxidant enzymes in cellular aging and degeneration

  • José Remacle
  • Carine Michiels
  • Martine Raes
Part of the EXS book series (EXS, volume 62)


Aerobic cells contain various amounts of the three main antioxidant enzymes: superoxide dismutase (SOD), catalase and GSH peroxidase. These three enzymes are necessary for cell survival since inhibition of their activity leads to the arrest of cell mitosis and to cell death. Amongst them, GSH peroxidase was shown to be more efficient than catalase and much more than SOD. This result was obtained by comparing the cell protection against oxidative stress after their microinjection in the cytoplasm. With age, the level of these antioxidant enzymes does not change in several experimental models, so that it is not possible to explain the aging process by a lack of protection due to a decrease in the activity of these three enzymes. However, tissues and cells are more susceptible to free radical attacks with age. In order to understand the importance of free radicals in this process, we have to distinguish between their respective effects on cell mitosis, cell death and cell aging. The effects on mitosis and cell death are well described, and the results clearly show a threshold of response which is determined by the antioxidant content of the cell. There is now evidence that short free radical stresses can also speed up the aging of in vitro cultured human fibroblasts. However, such effects are not typical of free radicals but are also obtained with many other deleterious substances so that free radicals have to be considered as one amongst other factors responsible for influencing the evolution of a cell to an older stage or to cell death. The lowering of the general metabolism and of the free energy in old cells are probably the main factors responsible for the increased susceptibility of these cells to stresses such as oxidative stresses.


Free Radical Antioxidant Enzyme Glutathione Peroxidase Human Fibroblast Antioxidant Molecule 
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  1. Ames, B. N., Cathart, R., Schwiers, E., and Cochstein, P. (1981) Uric acid: an antioxidant defence in human against oxidant and radical-caused aging and cancer. A hypothesis. Proc. Natl. Acad. Sci. USA 78: 6858–6862.CrossRefGoogle Scholar
  2. Balin, A. K., Goodman, D. B. P., Rasmussen, H., and Cristofalo, V. J. (1976) The effect of oxygen tension on the growth and the metaboUsm of WI-38 cells. J. Cell. Physiol. 89: 235–250.PubMedCrossRefGoogle Scholar
  3. Balin, A. K. (1982) Testing the free radical theory of aging, in: Testing the Theories of Ageing. R. Adelman and G. Roth, eds. Boca Raton, FL., CRC Press, pp. 137–182.Google Scholar
  4. Bayreuther, K., Rodemann, H. P., Hommel, R., Dittmann, K., Albiez, M., and Francz, P. I. (1988) Human skin fibroblasts in vitro differentiate along a terminal cell Uneage. Proc. Natl. Acad. Sci. USA 85: 5112.Google Scholar
  5. Cutler, R. G. (1982) Longevity is detemrined by specific genes: testing the hypothesis, in: Testing the Theories of Ageing. R. Adelman and G. Roth, eds. Boca Raton, FL., CRC Press, pp. 25–114.Google Scholar
  6. Cutler, R. G. (1985) Peroxide-producing potential of tissue: correlation with the longevity of mammalian species. Proc. Natl. Acad. Sci. USA 82: 4798–4802.PubMedCrossRefGoogle Scholar
  7. Cutler, R. G. (1991) Antioxidants and ageing. Am. J. Clin. Nutr. 53: 373S-379S.Google Scholar
  8. Elroy-Stein, O., Brenstein, Y., and Groner, Y. (1986) Overproduction of human Cu/Zn superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation. EMBO J. 5: 615–622.PubMedGoogle Scholar
  9. Freeman, B. A., and Crapo, J. D. (1982) Biology of disease. Free radicals and tissue injury. Lab. Invest. 47: 417–426.Google Scholar
  10. Hazelton, G., and Lang, C. (1980) Glutathione contents of tissues in the aging mouse. Biochem. J. 188: 25.Google Scholar
  11. Kellogg, E. W., and Fridovich, I. (1976) Superoxide dismutase in the rat and mouse as a function of age and longevity. J. Gerontol. 31: 405.PubMedGoogle Scholar
  12. Mbemba, F., Houbion, A., Raes, M., and Remade, J. (1985) Subcellular localization and modification with ageing of glutathione, glutathione peroxidase and glutathione reductase activities in human fibroblasts. Biochim. Biophys. Acta 838: 211–220.PubMedCrossRefGoogle Scholar
  13. Michiels, C., and Remade, J. (1988a) Use of the inhibition of enzymatic antioxidant systems in order to evaluate their physiological importance. Eur. J. Biochem. 177: 435–441.PubMedCrossRefGoogle Scholar
  14. Michids, C., Raes, M., Zachary, M.-D., Delaive, E., and Remade, J. (1988b) Microinjection of antibodies against superoxide dismutase and glutathione peroxidase. Exp. Cell Res. 179: 581–589.CrossRefGoogle Scholar
  15. Michiels, C., and Remade, J. (1988c) Quantitative study of natural antioxidant systems for cellular nitrofurantoin toxicity. Bjochim. Biophys. Acta 967: 341–347.CrossRefGoogle Scholar
  16. Michiels, C., Raes, M., Pigeolet, E., Corbisier, P., Lambert, D., and Remade, J. (1990a) Importance of a threshold for error accumulation in cell degenerative processes. I. Modulation of the threshold in a model of free radical-induced cell degeneration. Mech. Ageing Dev. 51: 41–54.PubMedCrossRefGoogle Scholar
  17. Michiels, C., Toussaint, O., and Remade, J. (1990b) Comparative study of oxygen toxicity in fibroblasts and endothelial cdls. J. Cdl. Physiol. 144: 295–302.Google Scholar
  18. Pigeolet, E., and Remade, J. (1991) Alteration of enzymes in ageing human fibroblasts in culture, v. Mechanisms of glutathione peroxidase modification. Mech. Ageing Dev. 58: 93–109.PubMedCrossRefGoogle Scholar
  19. Pinto, R. E., and Bartley, W. (1969) The effect of age and sex on GSSG reductase and glutathione peroxidase activities and on aerobic GSH oxidation in rat liver homogenates. Biochem. J. 112: 109–115.PubMedGoogle Scholar
  20. Raes, M., Michiels, C., and Remade, J. (1987) Comparative study of the enzymatic defense systems against oxygen-derived free radicals: the key role of glutathione peroxidase. Free Rad. Biol. Med. 3: 3–7.PubMedCrossRefGoogle Scholar
  21. Reis, U., and Gershon, D. (1976) Rat hver superoxide dismutase. Purification and age-related modifications. Eur. J. Biochem. 63: 617–62.CrossRefGoogle Scholar
  22. Remade, J., Houbion, A., and Houben, A. (1980) Subcellular fractionation of WI-38 fibroblasts comparison between young and old cells. Biochem. Biophys. Acta 630: 57–70.CrossRefGoogle Scholar
  23. Remade, J., Lenoir, G., Mbemba, P., Houben, A., Raes, M., Houbion, A., and Delaive, E. (1984) Pree radicals in cell degenerescence. Example of cellular ageing, in: New Trends on Atherosclerosis. C. L. Malmendier and J. Polanovski, eds. Fondations de recherche sur l’athérosclérose Belgium, pp. 23–29.Google Scholar
  24. Santa Maria, C., and Machado, A. (1987) Effect of development and ageing on pulmonary NADPH-cyt C reductase, glutathione peroxidase, glutathione reductase and thioredoxin reductase activities in male and female rats. Mech. Ageing Dev. 37: 183–195.CrossRefGoogle Scholar
  25. Seto, N. O. L., Hayashi, S., and Tener, G. M. (1990) Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect lifespan. Proc. Natl. Acad. Sci. USA 87: 4270–4274.PubMedCrossRefGoogle Scholar
  26. Somville, M., Houben, A., Raes, M., Houbion, A., Henin, V., and Remade, J. (1985) Alteration of enzymes in ageing human fibroblasts in culture. III Modification of superoxide dismutase as an environmental and reversible process. Mech. Ageing Dev. 29: 35–51.PubMedCrossRefGoogle Scholar
  27. Toussaint, O., Raes, M., and Remade, J. (1991) Aging as a multi-step process leading the cell from stage to stage characterized by a lowering of entropy production. Mech. Ageing Dev. 61: 45–64.PubMedCrossRefGoogle Scholar
  28. Ursini, F., Maiorino, M., and Gregolin, C. (1985) The selenoenzyme phosphohpid hydroperoxide glutathione peroxidase. Biochim. Biophys. Acta 839: 62–70.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 1992

Authors and Affiliations

  • José Remacle
    • 1
  • Carine Michiels
    • 1
  • Martine Raes
    • 1
  1. 1.Laboratoire de Biochimie CellulaireFacultés UniversitairesNamurBelgium

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