Öz
Aim: Paraoxonase-1 (PON1) whic is present in HDL structure, is an enzyme that decreases the oxidative stress in atherosclerotic lesions by preventing the HDL and LDL against to ox-idation. Thu study aims to determine the paraoxonase, arylesterase and lactonease activities of PON1 enzyme, taking into account the response of healthy subjects to the oral triglyceride tolerance test (OTTT).
Material and Method: Study group included 96 healthy subjects (45 female and 51 male with age range of 18-55 years). Study group was divided into three groups according to the area under curve (AUC) values calculated by using triglyceride levels at the fasting state and at 2nd, 4th and 6th hours after the high fat diet (OTTT). PON1 enzyme activity levels were determined by spectrofotometric methods. PON1 enzyme activities and other parameters in lower OTTT response group were compared to that of the upper group.
Results: Atherogenic lipid profile, increased total cholesterol and LDL-C and decreased HDL-C levels, was observed in subjects with the upper group men when compared to the lower group. PON1 lactonase activity was significantly lower in men than that of women (P<0.05). On the other hand, PON1 lactonase activity showed time-depended increase during OTTT in both sex. PON1 arylesterase activity in subjects with the upper group was significantly higher than that of the lower groups (P<0.022) in women.
Conclusion: It was observed that the upper groups with high OTTT response had an atherogenic lipid profile. It has been thought that PON1 enzyme activities tend to increase in the Postprandial period as a response to oxidative stress and detailed studies are needed.
Anahtar Kelimeler
Arilesterase Dyslipidemia High fat diet Lactonase Paraoxonase
Kaynakça
- 1. Hennekens CH. Increasing Burden of Cardiovascular Disease Current Knowledge and Future Directions for Research on Risk Factors. Circulation 1998 May 19;97(19):1995. PMID: 9531257
- 2. Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Song WF, Vickers KC. The role of lipids and lipoproteins in atherosclerosis. In Endotext [Internet]. MDText. 2019 Jan 3. PMID: 26844337
- 3. Cullen P, Funke H, Schulte H, Assmann G. Lipoproteins and cardiovascular risk-from genetics to CHD prevention. J Atheroscler Thromb. 1997;4(2):51-8. PMID: 9638514
- 4. Calabresi L, Gomaraschi M, Franceschini G. Endothelial protection by high-density lipoproteins: From bench to bedside. Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1724-31. PMID: 12969988
- 5. Contreras-Duarte S, Chen P, Andía M, Uribe S, Irarrázaval P, Kopp S, Kern S, Marsche G, Busso D, Wadsack CD, Rigotti A. Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice. Biol Res. 2018 Sep 15;51(1):34. PMID: 30219096
- 6. Beer S, Moren X, Ruiz J, James RW. Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects. Nutr Metab Cardiovasc Dis. 2006 Oct;16(7):457-65. PMID: 17015182
- 7. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human Serum Paraoxonase / Arylesterase ’ s Retained Hydrophobic N -Terminal Leader Sequence Associates With HDLs by Binding Phospholipids. Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2214-25. PMID: 10479665
- 8. Deakin S, Leviev I, Gomaraschi M, Calabresi L, Franceschini G, James RW. Enzy¬matically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem. 2002 Feb 8;277(6):4301-8. PMID: 11726658
- 9. Rodrigo L, Hernández AF, López-Caballero JJ, Gil F, Pla A. Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. Implications for its physiological role. Chem Biol Interact. 2001 Aug 31;137(2):123-37. PMID: 11551529
- 10. Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA, Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol. 1996 Apr;7(2):69-76. PMID: 8743898
- 11. Khersonsky O, Tawfik DS. The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases. J Biol Chem. 2006 Mar 17;281(11):7649-56. PMID: 16407305
- 12. de Vries MA, Klop B, Alipour A, van de Geijn GJ, Prinzen L, Liem AH, Valdivielso P, Rioja Villodres J, Ramírez-Bollero J, Castro Cabezas M. In vivo evidence for chylomicrons as mediators of postprandial inflammation. Atherosclerosis. 2015 Dec;243(2):540-5. PMID: 26523991
- 13. Liu HH, Li JJ. Aging and dyslipidemia: a review of potential mechanisms. Ageing Res Rev. 2015 Jan;19:43-52. PMID: 25500366
- 14. Ramírez-Vélez R. Postprandial lipemia induces endothelial dysfunction and higher insulin resistance in healthy subjects. Endocrinol Nutr. 2011 Dec;58(10):529-35. PMID: 22078763
- 15. Farinha JB, Macedo CEO, Rodrigues-Krause J, Krüger RL, Boeno FP, Macedo RCO, Queiroz JN, Teixeira BC, Reischak-Oliveira A. Effects of Two Combined Exercise Designs Associated With High-Fat Meal Consumption on Postprandial Lipemia, Insulinemia, and Oxidative Stress. J Strength Cond Res. 2018 May;32(5):1422-1430. PMID: 28486335
- 16. Ferretti G, Bacchetti T, Nègre-Salvayre A, Salvayre R, Dousset N, Curatola G. Structural modifications of HDL and functional consequences. Atherosclerosis. 2006 Jan;184(1):1-7. PMID: 16157342
- 17. Jackson KG, Poppitt SD, Minihane AM. Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis. 2012 Jan;220(1):22-33. PMID: 21955695
- 18. Patsch JR, Miesenböck G, Hopferwieser T, Mühlberger V, Knapp E, Dunn JK, Gotto AM Jr, Patsch W. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb. 1992 Nov;12(11):1336-45. PMID: 1420093
- 19. Cortés B, Núñez I, Cofán M, Gilabert R, Pérez-Heras A, Casals E, Deulofeu R, Ros E. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol. 2006 Oct 17;48(8):1666-71. PMID: 17045905
- 20. Guerci B, Paul JL, Hadjadj S, Durlach V, Vergès B, Attia N, Girard-Globa A, Drouin P. Analysis of the postprandial lipid metabolism: use of a 3-point test. Diabetes Metab. 2001 Sep;27(4 Pt 1):449-57. PMID: 11547218
- 21. Thomas AE, McKay DA, Cutlip MB. A nomograph method for assessing body weight. Am J Clin Nutr. 1976 Mar;29(3):302-4. PMID: 1258819
- 22. Singh D, Luis S. Ethnic and gender consensus for the effect of waist-to-hip ratio on judgment of women's attractiveness. Hum Nat. 1995 Mar;6(1):51-65. PMID: 24202830
- 23. Lindman AS, Veierød MB, Tverdal A, Pedersen JI, Selmer R. Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study. Eur J Epidemiol. 2010 Nov;25(11):789-98. PMID: 20890636
- 24. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007 Jul 18;298(3):299-308. PMID: 17635890
- 25. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007 Jul 18;298(3):309-16. PMID: 17635891
- 26. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005 Feb 15;69(4):541-50. PMID: 15670573
- 27. Richter RJ, Furlong CE. Determination of paraoxonase (PON1) status requires more than genotyping. Pharmacogenetics. 1999 Dec;9(6):745-53. PMID: 10634137
- 28. Fuhrman B, Volkova N, Aviram M. Paraoxonase 1 (PON1) is present in postprandial chylomicrons. Atherosclerosis. 2005 May;180(1):55-61. PMID: 15823275
- 29. Ferretti G, Bacchetti T. Effect of dietary lipids on paraoxonase-1 activity and gene expression. Nutr Metab Cardiovasc Dis. 2012 Feb;22(2):88-94. PMID: 22118836
- 30. 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 Mar 1;34(3):424-31. PMID: 20028357
Öz
Amaç: Paraoksonaz-1 (PON1) HDL yapısında bulunan, HDL ve LDL’yi oksidasyondan koruyarak aterosklerotik lezyonlardaki oksidatif stresi azaltan antioksidan bir enzimdir. Bu çalışmanın amacı, sağlıklı kişilerin oral trigliserid tolerans testine (OTTT) verdikleri cevaba göre PON1 enziminin paraoksonaz, arilesteraz ve laktonaz aktivitelerini değerlendirmektir.
Gereç ve Yöntem: Gönüllüler, yaşları 18-55 arasında değişen 45 kadın ve 51 erkek olmak üzere toplam 96 sağlıklı bireyden oluşmaktadır. Gönüllüler, açlık ve OTTT sonrası 2, 4 ve 6’ncı saatlerdeki TG seviyeleri kullanılarak hesaplanan eğri altındaki alan (AUC) değerlerine göre üç farklı gruba ayrılmıştır. PON1 enzim aktiviteleri ve diğer parametreler OTTT cevabı düşük olan grup ile yüksek olan grup arasında karşılaştırıldı. PON1 enzim aktiviteleri spektrofotometrik metodlarla belirlendi.
Bulgular: Erkeklerde üst grup ile alt grup karşılaştırıldığında aterojenik lipid profili, artmış total kolesterol ve LDL-K ile azalmış HDL-K düzeyleri gözlemlendi. PON1 laktonaz aktivitesi erkeklerde kadınlara göre anlamlı düşük bulundu (P<0.05). PON1 laktonaz aktivitesi her iki cinste de OTTT süresince zamana bağlı olarak artış gösterdi. Kadınlarda, üst grupta PON1 arilesteraz aktivitesi alt gruba göre anlamlı yüksek bulundu (P<0.022).
Sonuç: OTTT cevabı yüksek olan üst grupların aterojenik lipit profiline sahip oldukları gözlemlenmiştir. PON1 enzim aktivitelerinin oksidatif strese bir cevap olarak postprandial dönemde genellikle artış eğiliminde olduğu, ayrıntılı çalışmalara ihtiyaç duyulduğu düşünülmüştür.
Anahtar Kelimeler
Arilesteraz Dislipidemi Laktonaz Paraoksonaz Yüksek yağlı diyet
Kaynakça
- 1. Hennekens CH. Increasing Burden of Cardiovascular Disease Current Knowledge and Future Directions for Research on Risk Factors. Circulation 1998 May 19;97(19):1995. PMID: 9531257
- 2. Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Song WF, Vickers KC. The role of lipids and lipoproteins in atherosclerosis. In Endotext [Internet]. MDText. 2019 Jan 3. PMID: 26844337
- 3. Cullen P, Funke H, Schulte H, Assmann G. Lipoproteins and cardiovascular risk-from genetics to CHD prevention. J Atheroscler Thromb. 1997;4(2):51-8. PMID: 9638514
- 4. Calabresi L, Gomaraschi M, Franceschini G. Endothelial protection by high-density lipoproteins: From bench to bedside. Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1724-31. PMID: 12969988
- 5. Contreras-Duarte S, Chen P, Andía M, Uribe S, Irarrázaval P, Kopp S, Kern S, Marsche G, Busso D, Wadsack CD, Rigotti A. Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice. Biol Res. 2018 Sep 15;51(1):34. PMID: 30219096
- 6. Beer S, Moren X, Ruiz J, James RW. Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects. Nutr Metab Cardiovasc Dis. 2006 Oct;16(7):457-65. PMID: 17015182
- 7. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human Serum Paraoxonase / Arylesterase ’ s Retained Hydrophobic N -Terminal Leader Sequence Associates With HDLs by Binding Phospholipids. Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2214-25. PMID: 10479665
- 8. Deakin S, Leviev I, Gomaraschi M, Calabresi L, Franceschini G, James RW. Enzy¬matically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem. 2002 Feb 8;277(6):4301-8. PMID: 11726658
- 9. Rodrigo L, Hernández AF, López-Caballero JJ, Gil F, Pla A. Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. Implications for its physiological role. Chem Biol Interact. 2001 Aug 31;137(2):123-37. PMID: 11551529
- 10. Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA, Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol. 1996 Apr;7(2):69-76. PMID: 8743898
- 11. Khersonsky O, Tawfik DS. The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases. J Biol Chem. 2006 Mar 17;281(11):7649-56. PMID: 16407305
- 12. de Vries MA, Klop B, Alipour A, van de Geijn GJ, Prinzen L, Liem AH, Valdivielso P, Rioja Villodres J, Ramírez-Bollero J, Castro Cabezas M. In vivo evidence for chylomicrons as mediators of postprandial inflammation. Atherosclerosis. 2015 Dec;243(2):540-5. PMID: 26523991
- 13. Liu HH, Li JJ. Aging and dyslipidemia: a review of potential mechanisms. Ageing Res Rev. 2015 Jan;19:43-52. PMID: 25500366
- 14. Ramírez-Vélez R. Postprandial lipemia induces endothelial dysfunction and higher insulin resistance in healthy subjects. Endocrinol Nutr. 2011 Dec;58(10):529-35. PMID: 22078763
- 15. Farinha JB, Macedo CEO, Rodrigues-Krause J, Krüger RL, Boeno FP, Macedo RCO, Queiroz JN, Teixeira BC, Reischak-Oliveira A. Effects of Two Combined Exercise Designs Associated With High-Fat Meal Consumption on Postprandial Lipemia, Insulinemia, and Oxidative Stress. J Strength Cond Res. 2018 May;32(5):1422-1430. PMID: 28486335
- 16. Ferretti G, Bacchetti T, Nègre-Salvayre A, Salvayre R, Dousset N, Curatola G. Structural modifications of HDL and functional consequences. Atherosclerosis. 2006 Jan;184(1):1-7. PMID: 16157342
- 17. Jackson KG, Poppitt SD, Minihane AM. Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis. 2012 Jan;220(1):22-33. PMID: 21955695
- 18. Patsch JR, Miesenböck G, Hopferwieser T, Mühlberger V, Knapp E, Dunn JK, Gotto AM Jr, Patsch W. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb. 1992 Nov;12(11):1336-45. PMID: 1420093
- 19. Cortés B, Núñez I, Cofán M, Gilabert R, Pérez-Heras A, Casals E, Deulofeu R, Ros E. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol. 2006 Oct 17;48(8):1666-71. PMID: 17045905
- 20. Guerci B, Paul JL, Hadjadj S, Durlach V, Vergès B, Attia N, Girard-Globa A, Drouin P. Analysis of the postprandial lipid metabolism: use of a 3-point test. Diabetes Metab. 2001 Sep;27(4 Pt 1):449-57. PMID: 11547218
- 21. Thomas AE, McKay DA, Cutlip MB. A nomograph method for assessing body weight. Am J Clin Nutr. 1976 Mar;29(3):302-4. PMID: 1258819
- 22. Singh D, Luis S. Ethnic and gender consensus for the effect of waist-to-hip ratio on judgment of women's attractiveness. Hum Nat. 1995 Mar;6(1):51-65. PMID: 24202830
- 23. Lindman AS, Veierød MB, Tverdal A, Pedersen JI, Selmer R. Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study. Eur J Epidemiol. 2010 Nov;25(11):789-98. PMID: 20890636
- 24. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007 Jul 18;298(3):299-308. PMID: 17635890
- 25. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007 Jul 18;298(3):309-16. PMID: 17635891
- 26. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005 Feb 15;69(4):541-50. PMID: 15670573
- 27. Richter RJ, Furlong CE. Determination of paraoxonase (PON1) status requires more than genotyping. Pharmacogenetics. 1999 Dec;9(6):745-53. PMID: 10634137
- 28. Fuhrman B, Volkova N, Aviram M. Paraoxonase 1 (PON1) is present in postprandial chylomicrons. Atherosclerosis. 2005 May;180(1):55-61. PMID: 15823275
- 29. Ferretti G, Bacchetti T. Effect of dietary lipids on paraoxonase-1 activity and gene expression. Nutr Metab Cardiovasc Dis. 2012 Feb;22(2):88-94. PMID: 22118836
- 30. 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 Mar 1;34(3):424-31. PMID: 20028357
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 25 Nisan 2019 |
| Gönderilme Tarihi | 29 Ağustos 2018 |
| Kabul Tarihi | 20 Mart 2019 |
| Yayımlandığı Sayı | Yıl 2019 Cilt: 3 Sayı: 1 |
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