Skip to main content
SpringerLink
Log in
Book cover

The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism pp 199–206Cite as

Age-Related Alterations in PON1

  • Chapter

Part of the book series: Proteins And Cell Regulation ((PROR,volume 6))

Abstract

Aging is associated with an increased incidence of atherosclerosis. Atherosclerosis is an inflammatory disease initiated by oxidized low density lipoprotein (oxLDL). High density lipoprotein (HDL) is a powerful antioxidant protecting LDL and itself from oxidation as well by detoxifying the hydroperoxides from oxLDL. The enzyme responsible, at least in part, for this antioxidant effect of HDL is its tightly associated paraoxonase (PON1). As PON1 is responsible for the antioxidant effect of HDL and the atherosclerosis related cardiovascular diseases are increasing with aging an alteration either in the PON1 expression and/or activity should occur with aging. Indeed, PON1 serum concentrations do not change with aging while its activity significantly decreases. This chapter will describe the putative causes of this altered PON1 activity at the environmental and genetic levels. The possibility of PON1 activity modulation will be also discussed

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Augustinsson AB, Barr M. 1963, Age variation in plasma arylesterase activity in children. Clin Chim Acta 8:568–73.

    Article  CAS  PubMed  Google Scholar 

  • Aviram M, Kaplan M, Rosenblat M, Fuhrman B. 2005, Dietary antioxidants and paraoxonases against LDL oxidation and atherosclerosis development. Handb Exp Pharmacol. 170:263–300.

    CAS  PubMed  Google Scholar 

  • Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, Newton RS, La Du BN. 1999, Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic. Biol. Med. 26:892–904.

    Article  CAS  PubMed  Google Scholar 

  • Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. 1998, Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions: a possible peroxidative role for paraoxonase. J. Clin. Invest. 101:1581–1590.

    CAS  PubMed  Google Scholar 

  • Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington P.N. 1999, Serum paraoxonase after myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 19:330–335.

    CAS  Google Scholar 

  • Baum L, Ng HK, Woo KS, Tomlinson B, Rainer TH, Chen X, Cheung WS, Chan DK, Thomas GN, Tong CS, Wong KS. 2006, Paraoxonase 1 gene Q192R polymorphism affects stroke and myocardial infarction risk. Clin Biochem. Mar 39(3):191–5.

    Article  CAS  Google Scholar 

  • Bonafe M, Marchegiani F, Cardelli M, Olivieri F, Cavallone L, Giovagnetti S, Pieri C, Marra M, Antonicelli R, Troiano L, Gueresi P, Passeri G, Berardelli M, Paolisso G, Barbieri M, Tesei S, Lisa R, De Benedictis G, Franceschi C. 2002, Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians. Eur J Hum Genet. 10(5):292–6.

    Article  CAS  PubMed  Google Scholar 

  • Cherki M, Derouiche A, Drissi A, El Messal M, Bamou Y, Idrissi-Ouadghiri A, Khalil A, Adlouni A. 2005, Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: Intervention study in healthy men. Nutr Metab Cardiovasc Dis. 15(5):352–60.

    Article  PubMed  Google Scholar 

  • Cole TB, Jampsa RL, Walter BJ, Arndt TL, Richter RJ, Shih DM, Tward A, Lusis AJ, Jack RM, Costa LG, Furlong CE. 2003, Expression of human paraoxonase (PON1) during development. Pharmacogenetics 13:1–8.

    Article  Google Scholar 

  • Deakin SP, James RW. 2004, Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clinical Science 107:435–447.

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D. 2005, Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev. 126(2):351–61.

    Article  CAS  PubMed  Google Scholar 

  • Frey I, Berg A, Baumstark MW, Collatz KG, Keul J. 1990, Effects of age and physical performance capacity on distribution and composition of high-density lipoprotein subfractions in men. Eur J Appl Physiol Occup Physiol. 60(6):441–4.

    Article  CAS  PubMed  Google Scholar 

  • Fulop T Jr, Foris G, Worum I, Paragh G, Leovey A. 1985, Age related variations of some polymorphonuclear leukocyte functions. Mech Ageing Dev. 29(1):1–8.

    Article  Google Scholar 

  • Fulop T Jr, Fouquet C, Allaire P, Perrin N, Lacombe G, Stankova J, Rola-Pleszczynski M, Gagne D, Wagner JR, Khalil A, Dupuis G. 1997, Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev. 96(1–3):15–34.

    Article  Google Scholar 

  • Garin MC, James RW, Dussoix P, Blanche H, Passa P, Froguel P, Ruiz J. 1997, Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. J Clin Invest. 99(1):62–6.

    CAS  PubMed  Google Scholar 

  • Harman D. 1992, Role of free radicals in aging and disease. Ann. N Y Acad. Sci. 673:126–141.

    Article  CAS  PubMed  Google Scholar 

  • Heijmans BT, Westendorp RG, Lagaay AM, Knook DL, Kluft C, Slagboom PE. 2000, Common paraoxonase gene variants, mortality risk and fatal cardiovascular events in elderly subjects. Atherosclerosis 149(1):91–7.

    Article  CAS  PubMed  Google Scholar 

  • Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. 1993, The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet. 3(1):73–6.

    Article  CAS  PubMed  Google Scholar 

  • Jaouad L, de Guise C, Berrougui H, Cloutier M, Isabelle M, Fulop T, Payette H, Khalil A. 2006, Age-related decrease in high-density lipoproteins antioxidant activity is due to an alteration in the PON1’s free sulfhydryl groups. Atherosclerosis 185(1):191–200.

    Article  CAS  PubMed  Google Scholar 

  • Jarvik GP, Rozek LS, Brophy Hatsukami TS, Richter RJ, Schellenberg GD, Furlong CE. 2000, Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1(192) or PON1(55) genotype. Arterioscler. Thromb. Vasc. Biol. 20:2441–2447.

    CAS  PubMed  Google Scholar 

  • Jarvik GP, Trevanian N, Sai T, McKinstry LA, Wani R, Brophy VH, Richter RJ, Schellenberg GD, Heagerty PJ, Hatsukami TS, Furlong CE. 2002, Vitamins C and E intake is associated with increased paraoxonase activity. Arterioscler Thromb Vasc Biol. 22:1329–1333.

    Article  CAS  PubMed  Google Scholar 

  • Lenton KJ, Therriault H, Cantin AM, Fulop T, Payette H, Wagner JR. 2000, Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. Am J Clin Nutr 71(5):1194–200.

    CAS  PubMed  Google Scholar 

  • Lu CY, Lee HC, Fahn HJ, Wei YH. 1999, Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. Mutat Res. 423(1–2):11–21.

    CAS  PubMed  Google Scholar 

  • Mackness B, Mackness MI, Arrol S, Turkie W, Julier K, Abuasha B, Miller JE, Boulton AJ, Durrington PN. 1998, Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis 139(2):341–9.

    Article  CAS  PubMed  Google Scholar 

  • Mackness MI, Mackness B, Durrington PN, Fogelman AM, Berliner J, Lusis AJ, Navab M, Shih D, Fonarow GC. 1998, Paraoxonase and coronary heart disease. Curr Opin Lipidol. 9(4):319–24.

    Article  CAS  PubMed  Google Scholar 

  • Marchegiani F, Marra M, Spazzafumo L, James RW, Boemi M, Olivieri F, Cardelli M, Cavallone L, Bonfigli AR, Franceschi C. 2006, Jun;Paraoxonase activity and genotype predispose to successful aging. J Gerontol A Biol Sci Med Sci. 61(6):541–6.

    PubMed  Google Scholar 

  • Mertens A, Holvoet P. 2001, Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J. 15(12):2073–84.

    Article  CAS  PubMed  Google Scholar 

  • Milochevitch C, Khalil A. 2001, Study of the paraoxonase and platelet activating factor acetyl hydrolase activities with aging. Prostaglandins Leukot. Essent. Fatty Acids 65:241–246.

    Article  CAS  Google Scholar 

  • Mueller RF, Hornung S, Furlong CE, Anderson J, Giblett ER, Motulsky AG. 1983, Plasma paraoxonase polymorphism: a new enzyme assay, population, family, biochemical and linkage studies. Am J Hum Genet 35:393–408.

    CAS  PubMed  Google Scholar 

  • Olivieri F, Bonafe M, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M, Mugianesi E, Giampieri C, Moresi R, Stecconi R, Lisa R, Franceschi C. 2002, The -174 C/G locus affects in vitro/in vivo IL-6 production during aging. Exp Gerontol. 37(2–3):309–14.

    Article  CAS  PubMed  Google Scholar 

  • Ombres D, Pannitteri G, Montali A, Candeloro A, Seccareccia F, Campagna F, Cantini R, Campa PP, Ricci G, Arca M. 1998, The gln-Arg192 polymorphism of human paraoxonase gene is not associated with coronary artery disease in italian patients. Arterioscler Thromb Vasc Biol. 18(10):1611–6.

    Google Scholar 

  • Rea IM, McKeown PP, McMaster D, Young IS, Patterson C, Savage MJ, Belton C, Marchegiani F, Olivieri F, Bonafe M, Franceschi C. 2004, Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis. Exp Gerontol. 39(4): 629–35.

    Google Scholar 

  • Richter RJ, Furlong CE. 1999, Determination of paraoxonase (PON1) status requires more than genotyping. Pharmacogenetics. 9(6):745–53.

    Article  CAS  PubMed  Google Scholar 

  • Rozenberg O, Aviram M. 2006, S-Glutathionylation regulates HDL-associated paraoxonase 1 (PON1) activity. Biochem Biophys Res Commun. 351(2):492–8.

    Article  CAS  PubMed  Google Scholar 

  • Senti M, Tomas M, Vila J, Marrugat J, Elosua R, Sala J, Masia R. 2001, Relationship of age-related myocardial infarction risk and Gen/Arg 192 variants of the human paraoxonase 1 gene: the REGICOR study, Atherosclerosis 156:443–449.

    Google Scholar 

  • Seres I, Paragh G, Deschene E, Fulop T Jr, Khalil A. 2004, Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol. 39(1):59–66.

    Article  CAS  PubMed  Google Scholar 

  • Williams PD, Day T. 2003, Antagonistic pleiotropy, mortality source interactions, and the evolutionary theory of senescence. Evolution Int J Org Evolution. 57(7):1478–88.

    PubMed  Google Scholar 

  • Yashin AI, Ukraintseva SV, De Benedictis G, Anisimov VN, Butov AA, Arbeev K, Jdanov DA, Boiko SI, Begun AS, Bonafe M, Franceschi C. 2001, Have the oldest old adults ever been frail in the past? A hypothesis that explains modern trends in survival. J Gerontol A Biol Sci Med Sci. 56(10):B432–42.

    CAS  PubMed  Google Scholar 

  • Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, Steinberg D. 1989, Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest. 84(4):1086–95.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Medicine, Medical and Health Science Center, University of Debrecen, Hungary

    I. Seres

  2. Research Center on Aging, Département de Médecine, Service de Gériatrie Université de Sherbroooke, Sherbrooke, Qc, Canada

    T. Fulop & G. Paragh

Authors
  1. I. Seres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Fulop
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Paragh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Khalil
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Manchester, U.K

    Bharti Mackness

  2. University of Manchester, U.K

    Mike Mackness

  3. Technion Faculty of Medicine, Haifa, Israel

    Michael Aviram

  4. University of Debrecen, Hungary

    György Paragh

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer

About this chapter

Cite this chapter

Seres, I., Fulop, T., Paragh, G., Khalil, A. (2008). Age-Related Alterations in PON1. In: Mackness, B., Mackness, M., Aviram, M., Paragh, G. (eds) The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism. Proteins And Cell Regulation, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6561-3_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4020-6561-3_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-6560-6

  • Online ISBN: 978-1-4020-6561-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation