Relationship between paraoxonase and homocysteine: Crossroads of oxidative diseases

Archives of Medical Science

Volumn 8, Issue 1, 2012, Pages 138-153

  Yilmaz, Necat ^a  

^a Central Laboratories of Antalya Education and Research and Hospital of Ministry of Health   (Turkey)

Author keywords

Homocysteine; Homocysteine thiolactonase; Oxidative stress; Paraoxonase

Indexed keywords

ALBUMIN; ARYLDIALKYLPHOSPHATASE 1; ARYLDIALKYLPHOSPHATASE 2; ATORVASTATIN; BEZAFIBRATE; CARBONYL DERIVATIVE; CATECHIN; CYSTEINE; FENOFIBRATE; GEMFIBROZIL; GLUCONOLACTONASE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HOMOCYSTEINE; HOMOCYSTEINE THIOLACTONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; OMEGA 3 FATTY ACID; QUERCETIN; RADICAL; REACTIVE OXYGEN METABOLITE; SUPEROXIDE DISMUTASE; THIOL; THIOLACTONASE; THIYL RADICAL; UNCLASSIFIED DRUG;

ALCOHOL CONSUMPTION; AMINO ACID METABOLISM; ATHEROSCLEROSIS; CELL ENERGY; CHEMICAL REACTION; CHEMICAL STRUCTURE; CORONARY ARTERY ATHEROSCLEROSIS; DIABETES MELLITUS; DIABETIC RETINOPATHY; DNA POLYMORPHISM; DRUG MECHANISM; DRUG MEGADOSE; ENZYME ACTIVITY; ENZYME SUBSTRATE; HOMOCYSTEINYLATION; HUMAN; HYPERHOMOCYSTEINEMIA; LIPID PEROXIDATION; MEDICAL LITERATURE; METABOLIC DISORDER; NONHUMAN; NUTRITION; OXIDATION KINETICS; OXIDATIVE STRESS; PATHOPHYSIOLOGY; REVIEW; VASCULAR DISEASE;

EID: 84858219694     PISSN: 17341922     EISSN: None     Source Type: Journal    
DOI: 10.5114/aoms.2012.27294     Document Type: Review

References (135)

1. DuVigneaud V. A trail of research in sulfur chemistry and metabolism and related fields. Cornell University Press, Ithaca 1952; 25-56.
2. McCully KS. Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr 2007; 86: 1563S-8S. (Pubitemid 350126271)
3. Carson NAJ, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962; 37: 505-13.
4. Gerritsen T, Vaughn JG, Waisman HA. The identification of homocystine in the urine. Biochem Biophys Res Commun 1962; 9: 493-6.
5. Mudd SH, Finkelstein JD, Irreverre F, Laster L. Homocystinuria: an enzymatic defect. Science 1964; 143: 1443-5.
6. McCully KS. Homocysteine theory of arteriosclerosis: development and current status. In: Gotto AM Jr, Paoletti R (eds.). Atherosclerosis reviews. Vol 11. Raven Press, New York 1983; 157-246.
7. Jakubowski H. Pathophysiological consequences of homocysteine excess. J Nutr 2006; 136 (6 Suppl): 1741S-9S. (Pubitemid 43765390)
8. Jacobsen DW. Hyperhomocysteinemia and oxidative stress time for a reality check? Arterioscler Thromb Vasc Biol 2000; 20: 1182-4. (Pubitemid 30262915)
9. Yilmaz N, Eren E. Homocysteine oxidative stress and relation to bone mineral density in post-menopausal osteoporosis. Aging Clin Exp Res 2009; 21: 353-7.
10. Yilmaz N, Ciçek HK, Celik A, Meram I, Kocabas R, Davutoglu V. Diagnostic value of homocysteine, C-reactive protein and bilirubin for coronary artery disease. East Mediterr Health J 2007; 13: 522-35. (Pubitemid 47091258)
11. Yilmaz N, Kepkep N, Ciçek HK, Celik A, Meram I. Relation of parity and homocysteine to bone mineral density of postmenopausal women. Clin Lab 2006; 52: 49-56. (Pubitemid 43245865)
12. Naruszewicz M, Mirkewicz E, Olszewski AJ, McCully KS. Thiolation of low-density lipoproteins by homocysteine thiolactone causes increased aggregation and altered interaction with cultured macrophages. Nutr Metab Cardiovasc Dis 1994; 4: 70-7.
13. Undas A, Perla J, Lacinski M, Trzeciak WH, Kazmierski R, Jakubowski H. Autoantibodies against N-homo cysteinylated proteins in humans: implications for athe rosclerosis. Stroke 2004; 35: 1299-304. (Pubitemid 38697447)
14. Loscalzo J. The oxidant stress of hyperhomocysteinemia. J Clin Invest 1996; 98: 5-7.
15. Stamler JS, Osborne JA, Jaraki O, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993; 91: 308-18. (Pubitemid 23037286)
16. Suszynska J, Tisonczyk J, Lee HG, Smith MA, Jakubowski H. Reduced homocysteine-thiolactonase activity in Alzheimer's disease. J Alzheimers Dis 2010; 19: 1177.
17. Jakubowski H. The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease. J Physiol Pharmacol 2008; 59 Suppl 9: 155-67.
18. Misra HP. Generation of superoxide free radical during the autoxidation of thiols. J Biol Chem 1974; 249: 2151-5.
19. Nishio E, Watanabe Y. Homocysteine as a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for hydrogen peroxide. Br J Pharmacol 1997; 122: 269-74. (Pubitemid 27397198)
20. Lang D, Kredan MB, Moat SJ, et al. Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: role for superoxide anions. Arterioscler Thromb Vasc Biol 2000; 20: 422-7. (Pubitemid 30086099)
21. Doshi SN, McDowell IF, Moat SJ, et al. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol 2001; 21: 1196-202. (Pubitemid 34215150)
22. Mills BJ, Weiss MM, Lang CA, Liu MC, Ziegler C. Blood glutathione and cysteine changes in cardiovascular disease. J Lab Clin Med 2000; 135: 396-401.
23. Sibrian-Vazquez M, Escobedo JO, Lim S, Samoei GK, Strongin RM. Homocystamides promote free-radical and oxidative damage to proteins. Proc Natl Acad Sci U S A 2010; 107: 551-4.
24. Jakubowski H. Homocysteine is a protein amino acid in humans. Implications for homocysteine-linked disease. J Biol Chem 2002; 277: 30425-8. (Pubitemid 34970732)
25. Jakubowski H. Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 2000; 275: 3957-62. (Pubitemid 30094622)
26. Jakubowski H. Homocysteine-thiolactone and S-nitrosohomocysteine mediate incorporation of homocysteine into protein in humans. Clin Chem Lab Med 2003; 41: 1462-6. (Pubitemid 37493561)
27. Jakubowski H. Homocysteine thiolactone: metabolic origin and protein homocysteinylation in humans. J Nutr 2000; 130 (2 Suppl.): S377-81.
28. Williams KT, Schalinske KL. Homocysteine metabolism and its relation to health and disease. Biofactors 2010; 36: 19-24.
29. Chwatko G, Boers GH, Strauss KA, Shih DM, Jakubowski H. Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice. FASEB J 2007; 21: 1707-13. (Pubitemid 46855616)
30. Jakubowski H. Pathophysiological consequences of homocysteine excess. J Nutr 2006; 136 (6 Suppl): 1741S-9S. (Pubitemid 43765390)
31. Toohey JI. Homocysteine toxicity in connective tissue: theories, old and new. Connect Tissue Res 2008; 49: 57-61.
32. Morakinyo MK, Strongin RM, Simoyi RH. Modulation of homocysteine toxicity by S-nitrosothiol formation: a mechanistic approach. J Phys Chem B 2010; 114: 9894-904.
33. Koubaa N, Nakbi A, Hammami S, et al. Association of the C677T MTHFR polymorphism with homocysteine, ox-LDL levels, and thiolactonase activities in the severity of coronary syndrome. Clin Appl Thromb Hemost 2010; 16: 515-21.
34. Sikora M, Twardowski T, Jakubowski H. The role of homocysteine thiolactone in some of human diseases [Polish]. Postepy Biochem 2006; 52: 417-23.
35. Beltowski J, Wójcicka G, Jakubowski H. Modulation of paraoxonase 1 and protein N-homocysteinylation by leptin and the synthetic liver X receptor agonist T0901317 in the rat. J Endocrinol 2010; 204: 191-8.
36. Ferretti G, Bacchetti T, Masciangelo S, Bicchiega V. Effect of homocysteinylation on high density lipoprotein physico-chemical properties. Chem Phys Lipids 2010; 163: 228-35.
37. Undas A, Jankowski M, Twardowska M, Padjas A, Jakubowski H, Szczeklik A. Antibodies to N-homo cysteinylated albumin as a marker for early-onset coronary artery disease in men. Thromb Haemost 2005; 93: 346-50. (Pubitemid 40253742)
38. Jakubowski H, Perla-Kaján J, Finnell RH, et al. Genetic or nutritional disorders in homocysteine or folate meta bolism increase protein N-homocysteinylation in mice. FASEB J 2009; 23: 1721-7.
39. Chwatko G, Jakubowski H. Urinary excretion of homocysteine-thiolactone in humans. Clin Chem 2005; 51: 408-15. (Pubitemid 40175812)
40. Zimny J. Mechanisms that protect against homocysteine toxicity [Polish]. Postepy Biochem 2008; 54: 91-8.
41. Perna AF, Acanfora F, Luciano MG, et al. Plasma protein homocysteinylation in uremia. Clin Chem Lab Med 2007; 45: 1678-82. (Pubitemid 350232964)
42. Sikora M, Marczak L, Twardowski T, Stobiecki M, Jakubowski H. Direct monitoring of albumin lysine-525 N-homocysteinylation in human serum by liquid chromatography/mass spectrometry. Anal Biochem 2010; 405: 132-4.
43. Głowacki R, Bald E, Jakubowski H. Identification and origin of N-epsilon-homocysteinyl-lysine isopeptide in humans and mice. Amino Acids 2010; 39: 1563-9.
44. Perła-Kaján J, Marczak Ł, Kaján L, Skowronek P, Twar - dowski T, Jakubowski H. Modification by homo cysteine thiolactone affects redox status of cytochrome C. Biochemistry 2007; 46: 6225-31. (Pubitemid 46842865)
45. Roybal CN, Yang S, Sun CW, et al. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem 2004; 279: 14844-52. (Pubitemid 38618874)
46. Sauls DL, Lockhart E, Hoffman M. Reaction of fibrinogen with homocysteine thiolactone renders the resulting fibrin clots resistant to lysis. J Thromb Haemost 2005; 3 Suppl. 1: OR130.
47. Undas A, Brozek J, Jankowski M, Siudak Z, Szczeklik A, Jakubowski H. Plasma homocysteine affects fibrin clot permeability and resistance to lysis in human subjects. Arterioscler Thromb Vasc Biol 2006; 26: 1397-404. (Pubitemid 44305388)
48. Herrmann M, Tami A, Wildemann B, et al. Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone. Bone 2009; 44: 467-75.
49. Van Campenhout A, Moran CS, Parr A, et al. Role of homocysteine in aortic calcification and osteogenic cell differentiation. Atherosclerosis 2009; 202: 557-66.
50. Jakubowski H, Zhang L, Bardeguez A, Aviv A. Ho mocysteine thiolactone and protein homocys teinylation in human endothelial cells: implications for atherosclerosis. Circ Res 2000; 87: 45-51. (Pubitemid 30456934)
51. Jakubowski H. The molecular basis of homocysteine thiolactone-mediated vascular disease. Clin Chem Lab Med 2007; 45: 1704-16. (Pubitemid 350232966)
52. Perla-Kaján J, Twardowski T, Jakubowski H. Mechanisms of homocysteine toxicity in humans. Amino Acids 2007; 32: 561-72. (Pubitemid 46790938)
53. Sikora M, Jakubowski H. Homocysteine editing and growth inhibition in Escherichia coli. Microbiology 2009; 155: 1858-65.
54. Aldridge WN. Serum esterases I. Two types of esterase (A and B) hydrolysing p-nitrophenyl acetate, propionate and butyrate, and a method for their determination. Biochem J 1953; 53: 110-7.
55. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevent accumulation of hydroperoxides in low-density lipoprotein. FEBS Lett 1991; 286: 152-4.
56. Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 2005; 38: 153-63. (Pubitemid 39656127)
57. Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res 2005; 46: 1239-47. (Pubitemid 43109838)
58. Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet 1993; 3: 73-6. (Pubitemid 23063292)
59. Billecke S, Draganov D, Counsell R, et al. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 2000; 28: 1335-42.
60. Lacinski M, Skorupski W, Cieslinski A, Sokolowska J, Trzeciak WH, Jakubowski H. Determinants of ho mocysteine-thiolactonase activity of the paraoxonase-1 (PON1) protein in humans. Cell Mol Biol (Noisy-le-grand) 2004; 50: 885-93.
61. Loscalzo J. Paraoxonase and coronary heart disease risk: language misleads, linkage misinforms, function clarifies. Circ Cardiovasc Genet 2008; 1: 79-80.
62. Devarajan A, Bourquard N, Hama S, et al. Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antioxid Redox Signal 2010; 14: 341-51.
63. Zhang C, Peng W, Wang M, et al. Studies on protective effects of human paraoxonases 1 and 3 on atherosclerosis in apolipoprotein E knockout mice. Gene Ther 2010; 17: 626-33.
64. Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parma SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998; 101: 1581-90. (Pubitemid 28198486)
65. Draganov DI. Lactonases with oragnophosphatase activity: structural and evolutionary perspectives. Chem Biol Interact 2010; 187: 370-2.
66. Sutherland WH, de Jong SA, Walker RJ. Hypochlorous acid and low serum paraoxonase activity in haemodialysis patients: an in vitro study. Nephrol Dial Transplant 2004; 19: 75-82. (Pubitemid 38072618)
67. Rosenblat M, Gaidukov L, Khersonsky O, et al. The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux. J Biol Chem 2006; 281: 7657-65. (Pubitemid 43847536)
68. Otocka-Kmiecik A, Orłowska-Majdak M. The role of genetic (PON1 polymorphism) and environmental factors, especially physical activity, in antioxidant function of paraoxonase. Postepy Hig Med Dosw 2009; 63: 668-77.
69. Gur M, Yildiz A, Demirbag R, et al. Paraoxonase and arylesterase activities in patients with cardiac syndrome X, and their relationship with oxidative stress markers. Coron Artery Dis 2007; 18: 89-95.
70. Jakubowski H, Zhang L, Bardeguez A, Aviv A. Homocysteine thiolactone and protein homocys teinylation in human endothelial cells: implications for atherosclerosis. Circ Res 2000; 87: 45-51. (Pubitemid 30456934)
71. Billecke S, Draganov D, Counsell R, et al. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 2000; 28: 1335-42.
72. Ng CJ, Wadleigh DJ, Gangopadhyay A, et al. Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 2001; 276: 44444-9.
73. Huang RF, Huang SM, Lin BS, Wei JS, Liu TZ. Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci 2001; 68: 2799-811.
74. Zimny J, Sikora M, Guranowski A, Jakubowski H. Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase. J Biol Chem 2006; 281: 22485-92.
75. Yilmaz N, Cicek HK, Celik A, Davutoglu V. Diagnostic value of bilirubin concentrations compared with novel and traditional biomarkers in atherosclerosis with coronary artery disease. Saudi Med J 2006; 27: 1262-4. (Pubitemid 47045030)
76. van Himbergen TM, van Tits LJ, Roest M, Stalenhoef AF. The story of PON1: how an organophosphate-hydrolysing enzyme is becoming a player in cardiovascular medicine. Neth J Med 2006; 64: 34-8. (Pubitemid 43285584)
77. Shih DM, Gu L, Xia YR, et al. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998; 394: 284-7. (Pubitemid 28335041)
78. Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 2005; 38: 153-63. (Pubitemid 39656127)
79. Sonoki K, Iwase M, Sasaki N, et al. Relations of lysophosphatidylcholine in low-density lipoprotein with serum lipoprotein-associated phospholipase A2, paraoxo nase and homocysteine thiolactonase activities in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2009; 86: 117-23.
80. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 2005; 69: 541-50.
81. Adkins S, Gan KN, Mody M, La Du BN. Molecular basis for the polymorphic forms of human serum para oxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am J Hum Genet 1993; 52: 598-608. (Pubitemid 23311330)
82. Chwatko G, Jakubowski H. The determination of homocysteine-thiolactone in human plasma. Anal Biochem 2005; 337: 271-7. (Pubitemid 40187254)
83. Jakubowski H. Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci 2004; 61: 470-87. (Pubitemid 38316582)
84. Ciaccio M, Bellia C. Hyperhomocysteinemia and car diovascular risk: effect of vitamin supplementation in risk reduction. Curr Clin Pharmacol 2010; 5: 30-6.
85. Williams KT, Schalinske KL. Homocysteine metabolism and its relation to health and disease. Biofactors 2010; 36: 19-24.
86. Domagała TB, Łacinski M, Trzeciak WH, Mackness B, Mackness MI, Jakubowski H. The correlation of homocysteine-thiolactonase activity of the paraoxonase (PON1) protein with coronary heart disease status. Cell Mol Biol (Noisy-le-grand) 2006; 52: 4-10. (Pubitemid 46683309)
87. Mikael LG, Genest J Jr, Rozen R. Elevated homocysteine reduces apolipoprotein A-1 expression in hyper homocysteinemic mice and in males with coronary artery disease. Circ Res 2006; 98: 564-71.
88. Watts GF, Barrett PH, Chan DC. HDL metabolism in context: looking on the bright side. Curr Opin Lipidol 2008; 19: 395-404.
89. Bełtowski J. Protein homocysteinylation: a new mechanism of atherogenesis? Postepy Hig Med Dosw (Online) 2005; 59: 392-404.
90. Liao D, Yang X, Wang H. Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease. Clin Chem Lab Med 2007; 45: 1652-9. (Pubitemid 350232983)
91. Holven KB, Aukrust P, Rettersto/l K, et al. The anti-atherogenic function of HDL is impaired in hyperhomocysteinemic subjects. J Nutr 2008; 138: 2070-5.
92. Perla-Kaján J, Jakubowski H. Paraoxonase 1 protects against protein N-homocysteinylation in humans. FASEB J 2010; 24: 931-6.
93. Jakubowski H. The role of paraoxonase 1 in the detoxification of homocysteine thiolactone. Adv Exp Med Biol 2010; 660: 113-27.
94. Virtanen JK, Voutilainen S, Rissanen TH, et al. High dietary methionine intake increases the risk of acute coronary events in middle-aged men. Nutr Metab Cardiovasc Dis 2006; 16: 113-20. (Pubitemid 43384708)
95. Mackness MI, Mackness B, Durrington PN. Paraoxonase and coronary heart disease. Atheroscler Suppl 2002; 3: 49-55. (Pubitemid 38234486)
96. Weijun G, Juming L, Guoqing Y, et al. Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes. Adv Ther 2008; 25: 884-93.
97. Khersonsky O, Tawfik DS. Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. Biochemistry 2005; 44: 6371-82. (Pubitemid 40570731)
98. Gong M, Garige M, Varatharajalu R, et al. Quercetin upregulates paraoxonase 1 gene expression with concomitant protection against LDL oxidation. Biochem Biophys Res Commun 2009; 379: 1001-4.
99. Yang X, Gao Y, Zhou J, et al. Plasma homocysteine thiolactone adducts associated with risk of coronary heart disease. Clin Chim Acta 2006; 364: 230-4. (Pubitemid 43120647)
100. Jakubowski H, Ambrosius WT, Pratt JH. Genetic determinants ofhomocysteine thiolactonase activity in humans: implications for atherosclerosis. FEBS Lett 2001; 491: 35-9. (Pubitemid 32171996)
101. Koubaa N, Nakbi A, Hammami S, et al. Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome. Clin Biochem 2009; 42: 771-6.
102. Aydin M, Gokkusu C, Ozkok E, et al. Association of genetic variants in methylenetetrahydrofolate reductase and paraoxonase-1 genes with homocysteine, folate and vitamin B12 in coronary artery disease. Mol Cell Biochem 2009; 325: 199-208.
103. Man BL, Baum L, Fu YP, et al. Genetic polymorphisms of Chinese patients with ischemic stroke and concurrent stenoses of extracranial and intracranial vessels. J Clin Neurosci 2010; 17: 1244-7.
104. Lakshman MR, Gottipati CS, Narasimhan SJ, Munoz J, Marmillot P, Nylen ES. Inverse correlation of serum paraoxonase and homocysteine thiolactonase activities and antioxidant capacity of high-density lipoprotein with the severity of cardiovascular disease in persons with type 2 diabetes mellitus. Metabolism 2006; 55: 1201-6. (Pubitemid 44215939)
105. Marcucci R, Betti I, Cecchi E, et al. Hyperhomo cyste inemia and vitamin B6 deficiency: new risk markers for nonva lvular atrial fibrillation? Am Heart J 2004; 148: 456-61.
106. Shimano M, Inden Y, Tsuji Y, et al. Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation. Europace 2008; 10: 961-6.
107. Van Wagoner DR. Is homocysteine a mediator of atrial dysfunction or just another marker of endothelial dysfunction? Europace 2008; 10: 899-900.
108. Jiang X, Yang F, Brailoiu E, et al. Differential regulation of homocysteine transport in vascular endothelial andsmooth muscle cells. Arterioscler Thromb Vasc Biol 2007; 27; 1976-83. (Pubitemid 47312307)
109. Kerkeni M, Letaief A, Achour A, Miled A, Trivin F, Maaroufi K. Hyperhomocysteinemia, paraoxonase concen tration and cardiovascular complications in Tunisian patients with nondiabetic renal disease. Clin Biochem 2009; 42: 777-82.
110. Beltowski J, Wójcicka G, Jakubowski H. Modulation of paraoxonase 1 and protein N-homocysteinylation by leptin and the synthetic liver X receptor agonist T0901317 in the rat. J Endocrinol 2010; 204: 191-8.
111. Najib S, Sanchez-Margalet V. Homocysteine thiolactone inhibits insulin stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol 2005; 34: 119-26. (Pubitemid 40305554)
112. Kotani K, Sakane N, Sano Y, et al. Changes on the physiological lactonase activity of serum paraoxonase 1 by a diet intervention for weight loss in healthy overweight and obese women. Clin Biochem Nutr 2009; 45: 329-34.
113. Kosaka T, Yamaguchi M, Motomura T, Mizuno K. Investigation of the relationship between atherosclerosis and paraoxonase or homocysteine thiolactonase activity in patients with type 2 diabetes mellitus using a commercially available assay. Clin Chim Acta 2005; 359: 156-62. (Pubitemid 41116308)
114. Isbilen E, Yilmaz H, Arzu Ergen H, Unlucerci Y, Isbir T, Gurdol F. Association of paraoxonase 55 and 192 gene polymorphisms on serum homocysteine concentrations in preeclampsia. Folia Biol (Praha) 2009; 55: 35-40.
115. Barathi S, Angayarkanni N, Pasupathi A, et al. Homocysteinethiolactone and paraoxonase - novel markers of diabetic retinopathy. Diabetes Care 2010; 33: 2031-7.
116. Ateş O, Azizi S, Alp HH, et al. Decreased serum paraoxonase 1 activity and increased serum homo cysteine and malondialdehyde levels in age-related ma cular degeneration. Tohoku J Exp Med 2009; 217: 17-22.
117. Baskol G, Karakucuk S, Oner AO, et al. Serum paraoxonase 1 activity and lipid peroxidation levels in patients with age-related macular degeneration. Ophthalmologica 2006; 220: 12-6. (Pubitemid 41832689)
118. Ikeda T, Obayashi H, Hasegawa G, et al. Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration. Am J Ophthalmol 2001; 132: 191-5. (Pubitemid 32706513)
119. Angayarkanni N, Barathi S, Seethalakshmi T, et al. Serum PON1 arylesterase activity in relation to hyper homocysteinaemia and oxidative stress in young adult central retinal venous occlusion patients. Eye (Lond) 2008; 22: 969-74.
120. Mungan AG, Can M, Açikgöz S, Etürk E, Altinyazar C. Lipid peroxidation and homocysteine levels in Behçet's disease. Clin Chem Lab Med 2006; 44: 1115-8. (Pubitemid 44370933)
121. Leduc V, Théroux L, Dea D, Robitaille Y, Poirier J. Involvement of paraoxonase 1 genetic variants in Alzheimer's disease neuropathology. Eur J Neurosci 2009; 30: 1823-30.
122. Suszynska J, Tisonczyk J, Lee HG, Smith MA, Jakubowski H. Reduced homocysteine-thiolactonase activity in Alzheimer's disease. J Alzheimers Dis 2010; 19: 1177-83.
123. Wehr H, Bednarska-Makaruk M, Graban A, et al. Paraoxonase activity and dementia. Neurol Sci 2009; 283: 107-8.
124. Pasca̧ SP, Nemeş B, Vlase L, et al. High levels of homocysteine and low serum paraoxonase 1 ary lesterase activity in children with autism. Life Sci 2006; 78: 2244-8.
125. Paşca SP, Dronca E, NemeşB, et al. Paraoxonase 1 activities and polymorphisms in autism spectrum disorders. J Cell Mol Med 2010; 14: 600-7.
126. Noll C, Hamelet J, Ducros V, et al. Resveratrol supplementation worsen the dysregulation of genes involved in hepatic lipid homeostasis observed in hyperhomocysteinemic mice. Food Chem Toxicol 2009; 47: 230-6.
127. Varatharajalu R, Garige M, Leckey LC, Gong M, Lakshman MR. Betaine protects chronic alcohol and omega-3 PUFA-mediated down-regulations of PON1 gene, serum PON1 and homocysteine thiolactonase activities with restoration of liver GSH. Alcohol Clin Exp Res 2010; 34: 424-31.
128. Vasdev S, Gill V, Singal PK. Beneficial effect of low ethanol intake on the cardiovascular system: possible biochemical mechanisms. Vasc Health Risk Manag 2006; 2: 263-76. (Pubitemid 44275462)
129. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 2004; 107: 435-47. (Pubitemid 39506735)
130. Hamelet J, Aït-Yahya-Graison E, Matulewicz E, et al. Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice. Eur J Clin Invest 2007; 37: 933-8. (Pubitemid 350151181)
131. Hamelet J, Demuth K, Dairou J, et al. Effects of catechin on homocysteine metabolism in hyperhomocysteinemic mice. Biochem Biophys Res Commun 2007; 355: 221-7. (Pubitemid 46273391)
132. Gouédard C, Koum-Besson N, Barouki R, Morel Y. Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins. Mol Pharmacol 2003; 63: 945-56. (Pubitemid 36369002)
133. Bolayirli IM, Aslan M, Balci H, Altug T, Hacibekiroglu M, Seven A. Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine. Life Sci 2007; 81: 121-7. (Pubitemid 46921173)
134. Gaidukov L, Bar D, Yacobson S, et al. In vivo administration of BL-3050: highly stable engineered PON1-HDL complexes. BMC Clin Pharmacol 2009; 9: 18.
135. Stevens RC, Suzuki SM, Cole TB, Park SS, Richter RJ, Furlong CE. Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning. Proc Natl Acad Sci U S A 2008; 105: 12780-4.