PON1 arylesterase activity, HDL functionality and their correlation in malnourished children

2019 ◽  
Vol 32 (4) ◽  
pp. 321-326
Author(s):  
Mukund Ramchandra Mogarekar ◽  
Mahendrakumar Gajanan Dhabe ◽  
Mayuri Madhukarrao Palmate
Keyword(s):  
Lipid Profile ◽  
Lipid Hydroperoxide ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Ldl Oxidation ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Malnourished Children ◽  
Hdl Functionality

Abstract Background The study was done to assess high-density lipoprotein (HDL) functionality and to correlate this with paraoxonase 1 (PON1) activity in malnourished children. It aimed to find the effect of malnutrition on changes in PON1 activity, HDL functionality, lipid profile and lipid hydroperoxide formation. Methods This case control study included 30 malnourished children (up to age 5 years) and 30 healthy controls in the paediatric inpatient department of SRTR Government Medical College Ambajogai, India. Clinically diagnosed cases depending on anthropometric indices were selected. Serum PON1 activity by using phenyl acetate as a substrate, HDL functionality by haemin by its protection on H2O2 and haemin induced LDL oxidation, lipid profile by routine enzymatic methods and lipid hydroperoxide using the FOX2 assay were measured. Results Malnourished children had significantly decreased PON1 activity (106.6 ± 12.74** vs. 132.23 ± 28.49 IU/L), HDL functionality (116.55 ± 8** vs. 132.29 ± 10.9%), total cholesterol (TC) (102.5 ± 16** vs. 116.4 ± 12.65 mg/dL), HDL-cholesterol (C) (33.41 ± 9.74** vs. 40.55 ± 5.85 mg/dL) and reduced total protein level (5.56 ± 0.91* vs. 6.06 ± 1.055) higher triglycerides (TG) (146.76 ± 34.97* vs. 125.96 ± 17.21 mg/dL) level and total hydroperoxide (TPX) levels (5.568 ± 1.70** vs. 3.22 ± 1.52 μM/L). *p < 0.05 **p < 0.001. PON1 activity (r2 = 0.576) and TC (r2 = 0.567) shows significant positive correlation with HDL functionality. PON1 activity, HDL-C, HDL functionality and TPX shows independent contribution towards malnutrition in children in multivariate and univariate logistic regression. TC lost its significance in multivariate regression. Conclusions Malnutrition leads to decrease in HDL functionality and increase in hydroperoxide levels with a decrease in PON1 activity.

scholarly journals Serum paraoxonase-1 activity is associated with light to moderate alcohol consumption: the PREVEND cohort study

2018 ◽  
Vol 108 (6) ◽  
pp. 1283-1290 ◽  
Author(s):  
Eke G Gruppen ◽  
Stephan J L Bakker ◽  
Richard W James ◽  
Robin P F Dullaart
Keyword(s):  
Alcohol Consumption ◽  
Linear Regression Analysis ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Sensitivity ◽  
Population Based ◽  
Cross Sectional Study ◽  
Paraoxonase 1 ◽  
Phenyl Acetate ◽  
Cross Sectional

ABSTRACT Background Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated enzyme with antioxidative properties, which may protect against the development of cardiovascular disease. Alcohol consumption increases HDL cholesterol, but the extent to which alcohol consumption gives rise to higher serum PON-1 activity is uncertain. Objective In a population-based study, we determined the relation of serum PON-1 activity with alcohol consumption when taking account of HDL cholesterol and apolipoprotein A-I (apoA-I), its major apolipoprotein. Design A cross-sectional study was performed in 8224 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. Alcohol consumption was categorized as 1) no/rarely (25.3%); 2) 0.1–10 g/d (49.3%); 3) 10–30 g/d (20.1%); and 4) >30 g/d (5.2%) with 1 drink equivalent to 10 g alcohol. Serum PON-1 activity was measured as its arylesterase activity (phenyl acetate as substrate). Results Median serum PON-1 activity was 50.8, 53.1, 54.4, and 55.7 U/L in the 4 categories of alcohol consumption, respectively (P < 0.001). Its increase paralleled the increments in HDL cholesterol and apoA-I. Notably, there was no further increase in PON-1 activity, HDL cholesterol, and apoA-I when alcohol consumption was increased from 10–30 g/d to >30 g/d. Multivariable linear regression analysis demonstrated that PON-1 activity was related to alcohol consumption independently from clinical covariates, high sensitivity C-reactive protein, and lipid concentrations, including HDL cholesterol (P < 0.001 for each category of alcohol consumption with no alcohol consumption as the reference category). Notably, as inferred from standardized β-coefficients, there was no difference in PON-1 activity between 10–30 g alcohol/d and >30 g alcohol/d. Conclusions Alcohol consumption is associated with an increase in serum PON-1 activity, but its effect seems to reach a plateau with alcohol consumption of 10–30 g/d.

scholarly journals The association between PON1 gene polymorphisms (Q192R and L55M) and nephrotic syndrome in Iraqi children

2021 ◽  
Vol 2 (03) ◽  
pp. 118-130
Author(s):  
Raghad Ali ◽  
Rayah Baban ◽  
Shatha Ali
Keyword(s):  
Nephrotic Syndrome ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Healthy Controls ◽  
Coding Region ◽  
Pon1 Gene ◽  
Homozygous Genotype

Background: The role of paraoxonase 1 enzyme (PON1) and its single nucleotide polymorphisms (SNPs) in children with nephrotic syndrome (NS) has been reported previously in different ethnic and racial groups with divergent results. The human PON1 gene contains two coding region polymorphisms leading to two different PON1 isoforms. Objectives: The aim of the present study was to find out the association between the PON1 (Q192R and L55M) polymorphisms and their relation with serum PON1 activity as well as lipid profile tests (total cholesterol, TC; triglycerides, TG; high-density lipoprotein cholesterol, HDL-c; and low-density lipoprotein cholesterol, LDL-c) in children with NS. Methods: This study included a total of 80 participants (40 with NS in the age group of 2-14 years and 40 age and sex-matched healthy controls). The PON1 enzyme activity and lipid profile tests were measured in serum samples of all included participants. The PON1 genotype was determined by PCR-restriction enzyme fragment length polymorphism (PCR-RFLP) for both PON1 alleles (192 and 55) SNPs. Results: Our findings showed that the mean levels of lipid profile tests (TC, TG, LDL-c) were significantly increased in patients when compared with healthy controls (p<0.05), while the HDL-c concentration was significantly decreased in patients than that of controls. Also, the patients had significantly lower concentrations of PON1 when compared with the controls regardless of the genotype Q192R and L55M polymorphisms. Moreover, the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly frequent in patients when compared with the controls. Conclusions: Our results support that the presence of the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly higher in patients compared with the controls.

scholarly journals Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 899
Author(s):  
Jolanta Parada-Turska ◽  
Grażyna Wójcicka ◽  
Jerzy Beltowski
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Concentration ◽  
Serum Proteins ◽  
Density Lipoprotein ◽  
Cardiovascular Complications ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Control Subjects ◽  
Increased Risk

Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases.

Paraoxonase-1 (PON-1) genotype and activity and in vivo oxidized plasma low-density lipoprotein in Type II diabetes

2005 ◽  
Vol 109 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Mike J. Sampson ◽  
Simon Braschi ◽  
Gavin Willis ◽  
Sian B. Astley
Keyword(s):  
Type Ii Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Ldl Oxidation ◽  
Phenyl Acetate ◽  
Low Density ◽  
Type Ii

The HDL (high-density lipoprotein)-associated enzyme PON (paraoxonase)-1 protects LDL (low-density lipoprotein) from oxidative modification in vitro, although it is unknown if this anti-atherogenic action occurs in vivo. In a cross-sectional study of 58 Type II diabetic subjects and 50 controls, we examined the fasting plasma LDL basal conjugated diene concentration [a direct measurement of circulating oxLDL (oxidatively modified LDL)], lipoprotein particle size by NMR spectroscopy, PON-1 polymorphisms (coding region polymorphisms Q192R and L55M, and gene promoter polymorphisms −108C/T and −162G/A), PON activity (with paraoxon or phenyl acetate as the substrates) and dietary antioxidant intake. Plasma oxLDL concentrations were higher in Type II diabetic patients (males, P=0.048; females, P=0.009) and unrelated to NMR lipoprotein size, PON-1 polymorphisms or PON activity (with paraoxon as the substrate) in any group. In men with Type II diabetes, however, there was a direct relationship between oxLDL concentrations and PON activity (with phenyl acetate as the substrate; r=0.611, P=0.0001) and an atherogenic NMR lipid profile in those who were PON-1 55LL homozygotes. Circulating oxLDL concentrations in vivo were unrelated to PON-1 genotypes or activity, except in male Type II diabetics where there was a direct association between PON activity (with phenyl acetate as the substrate) and oxLDL levels. These in vivo data contrast with in vitro data, and may be due to confounding by dietary fat intake. Male Type II diabetic subjects with PON-1 55LL homozygosity have an atherogenic NMR lipid profile independent of LDL oxidation. These data do not support an in vivo action of PON on LDL oxidation.

scholarly journals Reduced Paraoxonase 1 Activity as a Marker for Severe Coronary Artery Disease

2013 ◽  
Vol 35 ◽  
pp. 97-103 ◽  
Author(s):  
Chiyan Zhou ◽  
Jia Cao ◽  
Liang Shang ◽  
Chuanfeng Tong ◽  
Hanling Hu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Potential Biomarker ◽  
Artery Disease

Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/−mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS  ≤ 40) (P<0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r=-0.393,P<0.001). PON1 activity may be a potential biomarker for the severity of CAD.

scholarly journals Oxidative Indices Correlate with Dyslipidemia and Pro-Inflammatory Cytokine Levels in Fluoride-Exposed Rats

2013 ◽  
Vol 64 (4) ◽  
pp. 521-529 ◽  
Author(s):  
Olusegun Kayode Afolabi ◽  
Emmanuel Bukoye Oyewo ◽  
Adeniran Sanmi Adekunle ◽  
Olaniyi Tope Adedosu ◽  
Adebayo Lawrence Adedeji
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Plasma Cholesterol ◽  
Interleukin 2 ◽  
Lipid Hydroperoxide ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Pon1 Activity ◽  
Pro Inflammatory Cytokines

Abstract The aim of this study was to establish the effects of fluoride on lipid metabolism and attendant inflammatory response by exposing rats to 50 mg L-1 and 100 mg L-1 of fluoride through drinking water for seven weeks. Both concentrations led to hypercholesterolemia while the 100 mg L-1 concentration induced hypertriglyceridaemia. High density lipoprotein (HDL) cholesterol levels dropped in the exposed rats while interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05). Fluoride-exposed rats also had significantly higher levels of liver malondialdehyde (MDA) and plasma lipid hydroperoxide (LOOH) but lower plasma paraoxonase (PON1) activity. Oxidative stress indices correlated with pro-inflammatory cytokines and plasma cholesterol. In contrast, proinflammatory cytokines inversely correlated with plasma triglyceride, HDL cholesterol and PON1. Our results suggest that the association between fluoride exposure with cardiovascular diseases may be related to its ability to disturb lipid homeostasis, and trigger pro-inflammatory cytokines and oxidative stress.

Paraoxonase 1 (PON1) and its relationship to lipid variables, age and gender in healthy volunteers

Biologia ◽  
2006 ◽  
Vol 61 (6) ◽  
Author(s):  
Katarína Sumegová ◽  
Pavel Blažíček ◽  
Bianca Fuhrman ◽  
Iveta Waczulíková ◽  
Zdeňka Ďuračková
Keyword(s):  
Lipid Profile ◽  
Serum Lipid ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Atherogenic Index ◽  
Paraoxonase 1 ◽  
Serum Lipid Profile ◽  
Positive Correlation ◽  
Paraoxonase Activity

AbstractRecent studies implied that low-density lipoprotein (LDL) modified predominantly by oxidation or glycation, significantly contributes to the formation of atherosclerotic lesions. In contrast to oxidized LDL (ox-LDL), high-density lipoprotein (HDL) is able to prevent accumulation of ox-LDL in arterial walls. This antiatherogenic property of HDL is attributed in part to several enzymes associated with the lipoprotein, including HDL-associated paraoxonase 1 (PON1). In this study we analyzed PON1 arylesterase/paraoxonase activities in relation to serum lipid profile, gender and age in thirty clinically healthy Slovak volunteers. Our results showed that PON1 arylesterase and paraoxonase activities were lower in citrated plasma than in serum by 16.6% and 27.3%, respectively. Among serum lipoproteins, only HDL-cholesterol level showed significant positive correlation with PON1 arylesterase activity (p = 0.042). Likewise, we found a significant relationship between atherogenic index (AI = total cholesterol/HDL-cholesterol) and PON1 arylesterase activity (p = 0.023). No significant correlation could be demonstrated between PON1 paraoxonase activity and serum lipid profile, age or gender. Furthermore, it was found that PON1 paraoxonase/arylesterase activities were higher in women compared with both investigated activities in men, but these differences were not statistically significant. These results confirmed a positive correlation between HDL-cholesterol and PON1 arylesterase activity. Moreover, it was found out that PON1 paraoxonase activity is not influenced either by gender or by age. PON1 arylesterase activity was however affected by gender to a limited extent.

scholarly journals Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 287 ◽  
Author(s):  
Veronica Tisato ◽  
Arianna Romani ◽  
Elisa Tavanti ◽  
Elisabetta Melloni ◽  
Daniela Milani ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Endogenous Factors ◽  
Factor Alpha

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated protein that endows its carrier with (lipo-)lactonase-dependent antioxidative features. Low levels of PON1 activity have been observed in association with obesity, a major risk factor for cardiovascular disease (CVD). Considering the well-recognized atheroprotective role of PON1, exogenous/endogenous factors that might modulate its levels/activity are raising great interest. Since adipokines represent a molecular link between obesity and CVD, we here explored the possible impact of these substances on PON1 activity/expression. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, monocyte chemoattractant protein-1, hepatocyte growth factor, resistin, leptin, and adiponectin were measured along with arylesterase, paraoxonase, and lactonase activities of PON1 in 107 postmenopausal women. Moreover, the direct effect of resistin on PON1 expression was evaluated in vitro. Multivariate analysis revealed that only resistin was significantly and inversely correlated with PON1-lactonase activities (r = −0.346, p < 0.001) regardless of confounding factors such as age or HDL-cholesterol. It is worth noting that no statistical link was found between adipokine and arylesterase or paraoxonase, the two promiscuous activities of PON1. Notably, resistin down-regulated PON1 expression occurred in hepatocellular carcinoma cultures. Our study suggests that resistin might be a negative modulator of PON1 expression and anti-oxidative activity.

scholarly journals Novel Associations of Nonstructural Loci with Paraoxonase Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ellen E. Quillen ◽  
David L. Rainwater ◽  
Thomas D. Dyer ◽  
Melanie A. Carless ◽  
Joanne E. Curran ◽  
...  
Keyword(s):  
Mexican American ◽  
San Antonio ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Activity Levels ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Novel Associations

The high-density-lipoprotein-(HDL-) associated esterase paraoxonase 1 (PON1) is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene,PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates—organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin—in 767 Mexican American individuals from San Antonio, Texas. Genetic influences on activity levels for each substrate were evaluated by association with approximately one million single nucleotide polymorphism (SNPs) while conditioning onPON1genotypes. Significant associations were detected at five loci including regions on chromosomes 4 and 17 known to be associated with atherosclerosis and lipoprotein regulation and loci on chromosome 3 that regulate ubiquitous transcription factors. These loci explain 7.8% of variation in PON1 activity with lactone as a substrate, 5.6% with the arylester, and 3.0% with paraoxon. In light of the potential importance ofPON1in preventing cardiovascular disease/events, these novel loci merit further investigation.

scholarly journals Paraoxonase 1 concerning dyslipidaemia, cardiovascular diseases, and mortality in haemodialysis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alicja E. Grzegorzewska ◽  
Paulina Adamska ◽  
Ewa Iwańczyk-Skalska ◽  
Kamila Ostromecka ◽  
Leszek Niepolski ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Hdl Cholesterol ◽  
Protein Product ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Cerebral Stroke ◽  
Adhesion Properties ◽  
Cholesterol Ratio ◽  
Atherogenic Dyslipidaemia ◽  
Uremic Patients

AbstractParaoxonase 1 (PON1) is known for preventing atherosclerosis through lipid-modifying features, antioxidant activity, anti-inflammatory, anti-apoptosis, anti-thrombosis, and anti-adhesion properties. Uremic patients requiring haemodialysis (HD) are especially prone to atherosclerosis and its complications. We analysed the PON1 gene (PON1) polymorphisms and serum PON1 (paraoxonase) activity concerning dyslipidaemia and related cardiovascular diseases and mortality to show how they associate under uremic conditions modified by maintenance HD treatment. The rs662 AA + AG (OR 1.76, 95%CI 1.10–2.80, P = 0.018), rs854560 TT (OR 1.48, 95%CI 1.04–2.11, P = 0.031), and rs854560 AT + TT (OR 1.28, 95%CI 1.01–1.63, P = 0.040) contributed to the prevalence of atherogenic dyslipidaemia diagnosed by the triglyceride (TG)/HDL-cholesterol ratio ≥ 3.8. The normalized serum PON1 activity positively correlated with atherogenic dyslipidaemia (ẞ 0.67 ± 0.25, P = 0.008). The PON1 rs854560 allele T was involved in the higher prevalence of ischemic cerebral stroke (OR 1.38, 1.02–1.85, P = 0.034). The PON1 rs705379 TT genotype contributed to cardiovascular (HR 1.27, 95% CI 1.03–1.57, P = 0.025) and cardiac (HR 1.34, 95% CI 1.05–1.71, P = 0.018) mortality. All P-values were obtained in multiple regression analyses, including clinical variables. Multifaceted associations of PON1 with dyslipidaemia, ischemic cerebral stroke, and cardiovascular mortality in HD patients provide arguments for the consideration of PON1 and its protein product as therapeutic targets in the prevention of atherosclerosis and its complications in uremic patients.

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