Clinical and Experimental Medicine

, Volume 8, Issue 1, pp 51–57

Relation of plasma protein oxidation parameters and paraoxonase activity in the ageing population



The incidence of atherosclerosis increases with age. Oxidative changes in proteins and lipids are considered to be among the molecular mechanisms leading to endothelial dysfunction. Paraoxonase (PON1) is exclusively associated with high-density lipoprotein (HDL) and protects both HDL and low-density lipoprotein (LDL) from oxidation. PON1 has two cysteine residues for its antioxidant function. We investigated the relation between PON1 activity and protein oxidation parameters such as protein hydroperoxides (P-OOH), protein carbonyl (PCO), total thiol (T-SH) and advanced oxidation protein products (AOPP). Our study also covered other oxidative stress parameters such as oxidised LDL (oxLDL) and superoxide dismutase activity in the plasma of young, middle-aged and elderly individuals. PON1 activity of elderly and middle-aged individuals was decreased significantly compared with that in the young group. oxLDL levels of elderly individuals were increased significantly compared with those of both the young and middle-aged individuals. P-OOH, PCO and AOPP levels of the elderly and middle aged individuals were higher compared with those of the young. On the other hand, T-SH levels of the elderly and middle-aged individuals were lower compared with those of the young. Side by side with the decrease in the T-SH levels in the middle-aged and elderly groups as compared to the young, the increase we have observed in other protein oxidation parameters in the groups leading to decreasing PON1 activity might, we think, create a predisposition to atherosclerosis.


Protein oxidation Thiol Paraoxonase Protein carbonyl Protein hydroperoxide Ageing 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Seres I, Paragh G, Deschene E et al (2004) Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol 39:59–66PubMedCrossRefGoogle Scholar
  2. 2.
    Lusis AJ (2000) Atherosclerosis. Nature 407:233–241PubMedCrossRefGoogle Scholar
  3. 3.
    Reaven PD, Napoli C, Merat S, Witztumc JI (2000) Lipoprotein modification and atherosclerosis in aging. Exp Gerontol 34:527–537CrossRefGoogle Scholar
  4. 4.
    Bonnefont-Rousselot D, Therond P, Beaudeux JL et al (1999) High density lipoproteins (HDL) and oxidative hypothesis of atherosclerosis. Clin Chem Lab Med 37:938–948CrossRefGoogle Scholar
  5. 5.
    Costa LG, Vitalone A, Cole TB, Furlong CE (2005) Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 69:541–550PubMedCrossRefGoogle Scholar
  6. 6.
    Watson AD, Berliner JA, Hama SY et al (1995) Protective effect of high density lipoprotein associated paraoxonase: inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96:2882–2891PubMedCrossRefGoogle Scholar
  7. 7.
    Gugliucci A, Lunceford N, Kinugasa E et al (2007) Acrolein inactivates paraoxonase 1: changes in free acrolein levels after hemodialysis correlate with increases in paraoxonase 1 activity in chronic renal failure patients. Clin Chim Acta 384:105–112PubMedCrossRefGoogle Scholar
  8. 8.
    Jaouad L, Guise C, Berrougui H et al (2006) Age-related decrease in high-density lipoproteins antioxidant activity is due to an alteration in the PON1’s free sulfhydryl groups. Atherosclerosis 185:191–200PubMedCrossRefGoogle Scholar
  9. 9.
    Woods AA, Linton SM, Davies MJ (2003) Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques. Biochem J 370:729–735PubMedCrossRefGoogle Scholar
  10. 10.
    Kaneda H, Taguchi J, Ogasawara K et al (2002) Increased level of advanced oxidation protein products in patients with coronary artery disease. Atherosclerosis 162:221–225PubMedCrossRefGoogle Scholar
  11. 11.
    Şkvařilová M, Bulava A, Stejskal D et al (2005) Increased level of advanced oxidation products (AOPP) as a marker of oxidative stress in patients with acute coronary syndrome. Biomed Papers 149:83–87Google Scholar
  12. 12.
    Stadtman ER (2004) Role of oxidant species in aging. Curr Med Chem 11:1105–1112PubMedGoogle Scholar
  13. 13.
    Çakatay U (2005) Protein oxidation parameters in type 2 diabetic patients with good and poor glycaemic control. Diabetes Metab 31:551–557PubMedCrossRefGoogle Scholar
  14. 14.
    Kalousová M, Zima T, Tesár V et al (2005) Advanced glycoxidation end products in chronic diseases-clinical chemistry and genetic background. Mutat Res 579:37–46PubMedGoogle Scholar
  15. 15.
    Capéillere-Blandin C, Gausson V, Descamps-Latscha B, Witko-Sarsat V (2004) Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim Biophys Acta 1689:91–102PubMedGoogle Scholar
  16. 16.
    — (2002) World Medical Association Declaration Helsinki: ethical principles for medical research involving human subjects. J Postgrad Med 48:206–208Google Scholar
  17. 17.
    Bridges AB, Fisher TC, Scot N et al (1992) Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers. Free Radic Res 16:89–97CrossRefGoogle Scholar
  18. 18.
    Hasselwander O, Savage DA, McMaster D et al (1999) Paraoxonase polymorphism are not associated with cardiovascular risk in renal transplants recipients. Kidney Int 56:289–298PubMedCrossRefGoogle Scholar
  19. 19.
    Saha N, Roy AC, Teo SH et al (1991) Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins. Clin Genet 40:277–282PubMedGoogle Scholar
  20. 20.
    Paragh G, Asztalos L, Seres I et al (1999) Serum paraoxonase activity changes in uremic and kidney transplanted patients. Nephron 83:126–131PubMedCrossRefGoogle Scholar
  21. 21.
    Eckerson HW, Romson J, Wyte C, La Du BN (1983) The human serum paraoxonase polymorphism: identification of phenotypes by their response to salts. Am J Hum Genet 35:214–227PubMedGoogle Scholar
  22. 22.
    Gay CA, Gebicki JM (2003) Measurement of protein and lipid hydroperoxides in biological systems by the ferric-xylenol orange method. Anal Biochem 315:29–35PubMedCrossRefGoogle Scholar
  23. 23.
    Zbikowska HM, Nowak P, Wachowicz B (2006) Protein modification caused by a high dose of gamma irradiation in cryo-sterilized plasma: Protective effects of ascorbate. Free Radic Biol Med 40:536–542PubMedCrossRefGoogle Scholar
  24. 24.
    Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363PubMedCrossRefGoogle Scholar
  25. 25.
    Hu ML (1994) Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 233:381–385Google Scholar
  26. 26.
    Witko-Sarsat V, Friedlander M, Capéillere-Blandin C et al (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313PubMedCrossRefGoogle Scholar
  27. 27.
    Çakatay U, Kayali R (2005) Plasma protein oxidation in aging rats after alpha-lipoic acid administration. Biogerontology 6:87–93PubMedCrossRefGoogle Scholar
  28. 28.
    Young IS, Woodside JV (2001) Antioxidants in health and disease. J Clin Pathol 54:176–186PubMedCrossRefGoogle Scholar
  29. 29.
    Alderman C, Shah S, Foreman JC et al (2002) The role of advanced oxidation protein products in regulation of dendritic cell function. Free Radic Biol Med 32:377–385PubMedCrossRefGoogle Scholar
  30. 30.
    Gieseg S, Duggan S, Gebicki JM (2000) Peroxidation of proteins before lipids in U937 cells exposed to peroxyl radicals. Biochem J 350:215–218PubMedCrossRefGoogle Scholar
  31. 31.
    Gebicki S, Gebicki JM (1999) Cross-linking of DNA and proteins induced by protein hydroperoxides. Biochem J 338:629–636PubMedCrossRefGoogle Scholar
  32. 32.
    Davies MJ, Fu S, Dean RT (1995) Protein hydroperoxides can give rise to reactive free radicals. Biochem J 305:643–649PubMedGoogle Scholar
  33. 33.
    Soszynski M, Filipiak A, Bartosz G, Gebicki JM (1996) Effect of amino acid peroxides on the erythrocyte. Free Radic Biol Med 20:45–51PubMedCrossRefGoogle Scholar
  34. 34.
    Eaton P (2006) Protein thiol oxidation in health and disease. Techniques for measuring disulfides and related modifications in complex protein mixtures. Free Radic Biol Med 40:1889–1899PubMedCrossRefGoogle Scholar
  35. 35.
    Morgan PE, Dean RT, Davies MJ (2005) Inhibition of glyceraldehyde-3-phosphate dehydrogenase by peptide and protein peroxides generated by singlet oxygen attack. Eur J Biochem 269:1916–1925CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2008

Authors and Affiliations

  1. 1.Şenesenevler Abdülezel Paşa Sk.IstanbulTurkey
  2. 2.Istanbul Faculty of Medicine Central Laboratory of Clinical BiochemistryIstanbul UniversityIstanbulTurkey
  3. 3.Cerrahpasa Medical Faculty Department of Pediatrics Laboratory of BiochemistryIstanbul UniversityIstanbulTurkey
  4. 4.Cerrahpasa Medical Faculty Department of BiochemistryIstanbul UniversityIstanbulTurkey

Personalised recommendations