The role of paraoxonases in the pathogenesis of inflammatory and infectious diseases and cancer


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Theparaoxonase (PON) gene family contains three members: PON1, PON2, and PON3. All the three members of the family possess antioxidant properties and lipo-lactonase activity, and play a role in the pathogenesis of many inflammatory diseases, including atherosclerosis, Alzheimer’s and Parkinson’s diseases, diabetes mellitus, and cancer. Recent studies have demonstrated that the intracellular paraoxonases PON2 and PON3 associated with mitochondria and mitochondria-associated endoplasmic reticulum membranes regulate mitochondrial superoxide production and prevent apoptosis. As oxidative stress is a result of mitochondrial dysfunction and is involved in the development of inflammatory diseases, including atherosclerosis and cancer, the studies of the enzymes PON2 and PON3 can initiate many epidemiological surveys conducted to search for a relationship between the paraoxonase genes and the development of many inflammatory diseases. Understanding these mechanisms will be able to introduce new treatments for oxidative stress-related diseases.

Full Text

Restricted Access

About the authors

Sergey A. Levakov

I.M. Sechenov First Moscow State Medical University

Natalya A. Sheshukova

I.M. Sechenov First Moscow State Medical University

Elizaveta A. Obukhova

I.M. Sechenov First Moscow State Medical University

Nadezhda V. Antipova

Academicians M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Peoples' Friendship University of Russia

Mikhail I. Shakhparonov

Academicians M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

References

  1. Duhig K., Chappell L.C., Shennan A.H. Oxidative stress in pregnancy and reproduction. Obstetric Medicine. 2016; 9(3): 113-6. doi: 10.1177/1753495X16648495
  2. Halliwell B., Gutteridge J.M.C. Free Radicals in Biology and Medicine. In: Halliwell, B. and Gutteridge, J.M.C., eds., Free Radicals in Biology and Medicine, 3rd Edition, Oxford University Press, Oxford. 1999: 1-25.
  3. Cadenas E., Davies K.J.A. Mitochondrial free radical generation, oxidative stress, and aging. Free Rad Biol Med. 2000; 29: 222-30. doi: 10.1016/s0891-5849(00)00317-8
  4. Furlong C.E., Marsillach J., Jarvik G.P., Costa L.G. Paraoxonases-1, -2 and -3: What are their functions? Chemico-Biological Interactions. Chem Biol Interact. 2016; 259(Pt B): 51-62. doi: 10.1016/j.cbi.2016.05.036.
  5. Ефимцева Э.А., Челпанова Т.И. Параоксоназа: молекулярно-генетические аспекты и клиническое значение. Успехи современной биологии. 2012; 132(3): 282-96. [Efimtseva E.A., Chelpanova T.I. Paraoxonase: Molecular Genetic Aspects and Clinical Value. Uspekhi sovremennoy biologii. 2012; 132(3): 282-96. (in Russian)].
  6. She Z.G., Chen H.Z, Yan Y., Li H., Liu D.P. The human paraoxonase gene cluster as a target in the treatment of atherosclerosis. Antioxid Redox Signal. 2012; 16: 597-632. doi: 10.1089/ars.2010.3774.
  7. Курдюков И.Д. Параоксоназа-1: генетические, биохимические и токсикологические аспекты. Профилактическая токсикология. 2011; 48-55. [Kurdukov I.D. Paraoxinase-1: genetic, biochemical and toxicological aspects. Profilakticheskaya toksikologiya. 2011; 48-55. (in Russian)].
  8. Garcia-Heredia A, Kensicki E., Mohney R.P., Rull A., Triguero I., Marsillach J., et al. Paraoxonase-1 deficiency is associated with severe liver steatosis in mice fed a high-fat high-cholesterol diet: a metabolomic approach. J Proteome Res. 2013; 12: 1946-55. doi: 10.1021/pr400050u
  9. Bhattacharyya T., Nicholls S.J., Topol E.J., Zhang R., Yang X., Schmitt D., et al. Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA. 2008; 299: 1265-76. doi: 10.1001/jama.299.11.1265.
  10. Stevens R.S., Suzuki S.M., Cole T.B., Park S.S., Richter R.J., Furlong C.E. Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning. Proc Natl Acad Sci USA. 2008; 105(35): 12780-4. doi: 10.1073/pnas.0805865105.
  11. Stoltz D.A., Ozer E.A., Ng C.J., Yu J.M., Reddy S.T., Lusis A.J., Bourquard N., Parsek M.R., Zabner J., Shih D.M. Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia. Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L852-60.
  12. Witte I., Foerstermann U., Devarajan A., Reddy S.T., Horke S. Protectors or Traitors: The Roles of PON2 and PON3 in Atherosclerosis and Cancer. J Lipids. 2012; 2012: 342806. doi: 10.1155/2012/342806.
  13. Schweikert E.M., Devarajan A., Witte I., Wilgenbus P., Amort J., Forstermann U., Shabazian A., Grijalva V., Shih D.M., Farias-Eisner R., Teiber J.F., Reddy S.T., Horke S. PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death. Cell Death Differ. 2012; 19: 1549-60. doi: 10.1038/cdd.2012.35.
  14. Ng C.J., Bourquard N., Grijalva V., Hama S., Shih D.M., Navab M., Fogelman A.M., Lusis A.J., Young S., Reddy S.T. Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem. 2006; 281: 29491-500. doi: 10.1074/jbc.M605379200
  15. Besler C., Heinrich K., Rohrer L., Doerries C., Riwanto M., Shih D.M., Chroni A., Yonekawa K., Stein S., Schaefer N., Mueller M., Akhmedov A., Daniil G., Manes C. Templin C., Wyss C., Maier W., Tanner F.C., Matter CM, Corti R, Furlong C, Lusis AJ, von Eckardstein A., Fogelman A.M., Luscher T.F., Landmesser U. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011; 121(7): 2693-708. doi: 10.1172/JCI42946.
  16. Huang Y., Wu Z., Riwanto M., Gao S., Levison B. S., Gu X., et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. J Clin Invest. 2013; 123(9): 3815-28. http://doi.org/10.1172/JCI67478
  17. Levy E., Trudel K., Bendayan M., Seidman E., Delvin E., Elchebly M., Lavoie J.C., Precourt L.P., Amre D., Sinnett D. Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats, Am J Physiol Gastrointest Liver Physiol. 2007; 293(6): G1252-61. doi: 10.1152/ajpgi.00369.2007
  18. Devarajan A., Bourquard N., Hama S., Navab M., Grijalva V.R., Morvardi S., Clarke C.F., Vergnes L., Reue K., Teiber J.F., Reddy S.T. Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis, Antioxid Redox Signal. 2011; 14: 341-51. doi: 10.1089/ ars.2010.3430.
  19. Horke S., Witte I., Wilgenbus P., Altenhofer S., Kruger M., Li H., Forstermann U. Protective effect of paraoxonase-2 against endoplasmic reticulum stress-induced apoptosis is lost upon disturbance of calcium homoeostasis. Biochem J. 2008; 416(3): 395-405. doi: 10.1042/BJ20080775.
  20. Reddy S.T., Wadleigh D.J., Grijalva V., Ng C., Hama S., Gangopadhyay A., Shih D.M., Lusis A.J., Navab M. Fogelman A.M. Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol. 2001; 21: 542-7. doi: 10.1161/01.atv.21.4.542
  21. Боровкова Е.И., Антипова Н.В., Корнеенко Т.В., Шахпаронов М.И., Боровков И.М. Параоксоназа: универсальный фактор антиоксидантной защиты организма человека. Вестник Российской академии медицинских наук. 2017; 72(1): 5-10. https://doi.org/10.15690/ vramn764
  22. Devarajan A., Shih D., Reddy S.T. Inflammation, Infection, Cancer and All That..The Role of Paraoxonases. Advances in Experimental Medicine and Biology. 2014; 824: 33-41. http://doi.org/10.1007/978-3-319-07320-0_5
  23. Kim D.S., Marsillach J., Furlong C.E., Jarvik G.P. Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease. Pharmacogenomics. 2013; 14(12): 1495-1515. http://doi.org/10.2217/ pgs.13.147
  24. Schweikert E.-M., Amort J., Wilgenbus P., Forstermann U., Teiber J. F., Horke S. Paraoxonases-2 and -3 Are Important Defense Enzymes against Pseudomonas aeruginosa Virulence Factors due to Their Anti-Oxidative and AntiInflammatory Properties. J Lipids. 2012; 2012: 352857. http://doi.org/10.1155/ 2012/352857.1155/2012/352857
  25. Bacchetti T., Ferretti G., Sahebkar A. The role of paraoxonase in cancer. Semin. Cancer Biol. 2017; 56: 72-86. doi: 10.1016/j.semcancer.2017.11.013.
  26. Шахпаронов М.И., Антипова Н.В., Шендер В.О., Шнайдер П.В., Арапиди Г.П., Песто Н.Б., Павлюков М.С. Экспрессия и внутриклеточная локализация параоксоназы 2 в опухолевых клетках различного типа. Acta Naturae. 2018; 10(3): 100-7.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies