Paraoxonase-1 activities in children and adolescents with type 1 diabetes mellitus

• Authors: Elena Craciun , Daniel Leucuta , Razvan Rusu , Bianca David , Victoria Cret , Eleonora Dronca
• Languages of publication: EN

Abstracts

EN

Background: Paraoxonase-1 is an HDL-associated esterase that acts as an anti-atherogenic agent by protecting LDL from oxidation. This study investigates paraoxonase-1 activities in children and adolescents with type 1 diabetes mellitus and possible associations with other biochemical markers. Patients and methods: The study enrolled 82 children and adolescents with type 1 diabetes mellitus and 41 controls with similar age and gender distribution. Serum paraoxonase-1 arylesterase and salt-stimulated paraoxonase activities were assessed by measuring the rates of phenyl acetate and paraoxon hydrolysis, respectively; paraoxonase-1 lactonase activity and oxidized LDL were assessed by a pH-sensitive colorimetric assay and ELISA, respectively. Glycated haemoglobin HbA1c and lipid profile were assayed with an immunoturbidimetric method and commercially available kits, respectively. Results: We found lower paraoxonase-1 activities in diabetics when compared to controls. The decrease was statistically significant only for the lactonase activity, the difference being higher when referring to the subgroup with poor glycaemic control. The lactonase activity/HDL ratio was also lower in diabetics vs. controls, but without statistical significance. Both lactonase and arylesterase activities were negatively correlated with HbA1c in diabetics, but only the latter was statistically significant (ρ = -0.21, P = 0.055; ρ = -0.24, P = 0.03, respectively). A correlation coefficient of ρ = 0.196 (P = 0.078) was found between oxidized LDL and HbA1c. Conclusion: All paraoxonase-1 activities were lower in diabetic children and adolescents, but only the decrease in the lactonase activity was statistically significant. Although lipid profile and glycaemic control were altered in diabetics, no differences were observed between groups regarding oxidized LDL level.

Keywords

EN

paraoxonase-1; lactonase; arylesterase; children; type 1 diabetes mellitus

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2016
• Volume: 63
• Issue: 3
• Pages: 511-515

Dates

published

2016

received

2015-10-30

revised

2016-04-08

accepted

2016-05-21

(unknown)

2016-06-23

Contributors

author

Elena Craciun

• Department of Pharmaceutical Biochemistry and Clinical Laboratory, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

author

Daniel Leucuta

• Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

author

Razvan Rusu

• Department of Molecular Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

author

Bianca David

• Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

author

Victoria Cret

• Paediatric Emergency County Hospital, 1th Paediatric Clinic, Cluj-Napoca, Romania

author

Eleonora Dronca

• Department of Molecular Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

References

• Abbott CA, Mackness MI, Kumar S, Boulton AJ, Durrington PN (1995) Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 15: 1812-1818.
• Aharoni S, Aviram M, Fuhrman B (2013) Paraoxonase 1 (PON1) reduces macrophage inflammatory responses. Atherosclerosis 228: 353-361. doi: 10.1016/j.atherosclerosis.2013.03.005.
• 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.
• Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48: 1-9.
• Ben-David M, Elias M, Filippi JJ, Duñach E, Silman I, Sussman JL, Tawfik DS (2012) Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1. J Mol Biol 418: 181-196. doi: 10.1016/j.jmb.2012.02.042.
• Boemi M, Leviev I, Sirolla C, Pieri C, Marra M, James RW (2001) Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation. Atherosclerosis 155: 229-235.
• Eckerson HW, Wyte CM, La Du B (1983) The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 35: 1126-1138.
• Ferretti G, Bacchetti T, Busni D, Rabini RA, Curatola G (2004) Protective effect of paraoxonase activity in high-density lipoproteins against erythrocyte membranes peroxidation: A comparison between healthy subjects and type 1 diabetic patients. J Clin Endocrinol Metab 89: 2957-2962.
• Flekac M, Skrha J, Zidkova K, Lacinova Z, Hilgertova J (2008) Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiol Res 57: 717-726.
• Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499-502.
• Hamad A, Hasan S, Qureshi HJ, Sami W (2010) Assessment of oxidized low density lipoprotein, as atherosclerosis risk marker in type 1 diabetic children with short history of diabetes mellitus. Pak J Physiol 6: 32-35.
• Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS (2004) Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 11: 412-419.
• James RW (2006) A long and winding road: defining the biological role and clinical importance of paraoxonases. Clin Chem Lab Med 44: 1052-1059.
• Khersonsky O, Tawfik DS (2005) Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. Biochemistry 44: 6371-6382.
• Kordonouri O, James RW, Bennetts B, Chan A, Kao YL, Danne T, Silink M, Donaghue K (2001) Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus. Metabolism 50: 657-660.
• Li R, Oteiza A, Sørensen KK, McCourt P, Olsen R, Smedsrød B, Svistounov D (2011) Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins. Am J Physiol Gastrointest Liver Physiol 300: G71-G81. doi: 10.1152/ajpgi.00215.2010.
• Mackness B, Durrington PN, Boulton AJ, Hine D, Mackness MI (2002) Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls. Eur J Clin Invest 32: 259-264.
• Mackness M, Mackness B (2013) Targeting paraoxonase-1 in atherosclerosis. Expert Opin Ther Targets 17: 829-837. doi: 10.1517/14728222.2013.790367.
• Mastorikou M, Mackness B, Liu Y, Mackness M (2008) Glycation of paraoxonase-1 inhibits its activity and impairs the ability of high-density lipoprotein to metabolize membrane lipid hydroperoxides. Diabet Med 25: 1049-1055. doi: 10.1111/j.1464-5491.2008.02546.x.
• Nair SP, Shah NC, Taggarsi A, Nayak U (2011) PONI and its association with oxidative stress in type I and type II diabetes mellitus. Diabetes Metab Syndr 5: 126-129. doi: 10.1016/j.dsx.2012.02.022.
• Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST (2005) The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 38: 153-163.
• Nguyen SD, Hung ND, Cheon-Ho P, Ree KM, Dai-Eun S (2009) Oxidative inactivation of lactonase activity of purified human paraoxonase 1 (PON1). Biochim Biophys Acta 1790: 155-160. doi: 10.1016/j.bbagen.2008.11.009.
• R Development Core Team (2010) R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, Available at. http://www.R-project.org.
• Rosenblat M, Gaidukov L, Khersonsky O, Vaya J, Oren R, Tawfik DS, Aviram M (2006) 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 281: 7657-7665.
• Rosenblat M, Karry R, Aviram M (2006) Paraoxonase 1 (PON1) is a more potent antioxidant and stimulant of macrophage cholesterol efflux, when present in HDL than in lipoprotein-deficient serum: relevance to diabetes. Atherosclerosis 187: 74-81.
• Ross R (1986) The pathogenesis of atherosclerosis - an update. N Engl J Med 314: 488-500.
• Rozenberg O, Rosenblat M, Coleman R, Shih DM, Aviram M (2003) Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice. Free Radic Biol Med 34: 774-784.
• Rozenberg O, Shiner M, Aviram M, Hayek T (2008) Paraoxonase 1 (PON1) attenuates diabetes development in mice through its antioxidative properties. Free Radic Biol Med 44: 1951-1959. doi: 10.1016/j.freeradbiomed.2008.02.012.
• She ZG, Chen HZ, Yan Y, Li H, Liu DP (2012) The human paraoxonase gene cluster as a target in the treatment of atherosclerosis. Antioxid Redox Signal 16: 597-632. doi: 10.1089/ars.2010.3774.
• Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, Cheroutre H, Faull KF, Berliner JA, Witztum JL, Lusis AJ (2000) Combined serum paraoxonase knockout/apolipoprotein e knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275: 17527-17535.
• Valabhji J, McColl AJ, Schachter M, Dhanjil S, Richmond W, Elkeles RS (2001) High-density lipoprotein composition and paraoxonase activity in Type I diabetes. Clin Sci (Lond) 101: 659-670.

Identifiers

DOI

10.18388/abp.2015_1209