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.

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.

Impaired Antiatherogenic Functions of High-density Lipoprotein in Patients with Ankylosing Spondylitis

2015 ◽  
Vol 42 (9) ◽  
pp. 1652-1660 ◽  
Author(s):  
Christina Gkolfinopoulou ◽  
Efstratios Stratikos ◽  
Dimitris Theofilatos ◽  
Dimitris Kardassis ◽  
Paraskevi V. Voulgari ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
High Density Lipoprotein ◽  
Antioxidant Capacity ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Akt Kinase ◽  
Increased Risk

Objective.Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with increased risk of cardiovascular disease (CVD). High-density lipoprotein (HDL) exerts a series of antiatherogenic properties and protects from CVD. We evaluated whether HDL antiatherogenic properties are impaired in patients with AS.Methods.HDL (apoB-depleted serum) was isolated from 35 patients with AS and 35 age- and sex-matched controls. We measured the antioxidant capacity of HDL, the ability of HDL to induce cholesterol efflux, the activity of HDL-associated enzymes paraoxonase-1 (PON1) and myeloperoxidase (MPO), as well as the ability of HDL to induce Akt kinase activation.Results.HDL from patients with AS had decreased antioxidant capacity and decreased ability to promote cholesterol efflux from macrophages compared to controls. HDL-associated PON1 activity was lower and HDL-associated MPO activity higher in patients with AS compared to controls. Higher MPO activity correlated positively with lower antioxidant capacity of HDL in patients with AS. In addition, HDL from patients with AS had impaired endothelial Akt kinase activating properties that were inversely correlated with the MPO/PON1 ratio and positively correlated with the cholesterol efflux capacity of HDL.Conclusion.HDL from patients with AS displays impaired antiatherogenic properties. Attenuation of HDL properties may constitute a link between AS and CVD.

Association of Dyslipidemia, Oxidative Stress, and Inflammation With Redox Status in VLDL, LDL, and HDL Lipoproteins in Patients With Renal Disease

Angiology ◽  
2018 ◽  
Vol 69 (10) ◽  
pp. 861-870 ◽  
Author(s):  
Milica Miljkovic ◽  
Aleksandra Stefanovic ◽  
Sanja Simic-Ogrizovic ◽  
Jelena Vekic ◽  
Natasa Bogavac-Stanojevic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Redox Status ◽  
Cardiovascular Complications ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Density

Some cardiovascular complications in patients with chronic kidney disease and end-stage renal disease may be caused by structurally and functionally modified lipoproteins. Redox status (advanced oxidation protein products [AOPPs]), prooxidant–antioxidant balance, total protein sulfhydryl (SH-groups), and paraoxonase 1 (PON1) activity were assessed in 77 renal patients and 20 controls. Lipoproteins were isolated using ultracentrifugation. PON1, PON3, and pentraxin-3 concentration were determined by enzyme-linked immunosorbent assay (ELISA). Dyslipidemia-Oxy-Inflammation (DOI) score was calculated as a sum of dyslipidemia, oxidative stress, and inflammation scores. The dyslipidemia score ( P < .001), oxy score ( P < .01), inflammation score (P < .001), and the DOI score ( P < .001) were higher in patient groups compared with controls. The very-low-density lipoprotein (VLDL) fraction contained the highest amount of AOPP ( P < .001) compared with other lipoprotein fractions in all groups. The low-density lipoprotein (LDL) fraction contained elevated AOPP in all groups compared with the high-density lipoprotein (HDL) fraction ( P < .001). Significant positive correlation was observed between AOPP in LDL fraction and DOI score (ρ = 0.510, P < .01). Dyslipidemia, oxidative stress, and inflammation play an interactive role in renal disease and are mutually associated with redox status in VLDL, LDL, and HDL lipoproteins in plasma of renal patients.

scholarly journals Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis

2012 ◽  
Vol 35 (3) ◽  
pp. 144 ◽  
Author(s):  
Abdolkarim Mahrooz ◽  
Mehryar Zargari ◽  
Omid Sedighi ◽  
Hamed Shaygani ◽  
Ghorban Gohari
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pon1 Activity ◽  
Control Group ◽  
Control Subjects ◽  
Increased Risk ◽  
The Status ◽  
Serum Paraoxonase ◽  
Esrd Patients

Purpose: Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors. Methods: Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre-and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay. Results: Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre-dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD. Conclusions: Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD.

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 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 Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High-Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease

2016 ◽  
Vol 68 (6) ◽  
pp. 1367-1376 ◽  
Author(s):  
Javier Rodríguez-Carrio ◽  
Raquel López-Mejías ◽  
Mercedes Alperi-López ◽  
Patricia López ◽  
Francisco J. Ballina-García ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1

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 Could Omega 3 Fatty Acids Preserve Muscle Health in Rheumatoid Arthritis?

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 223
Author(s):  
Kassandra Lanchais ◽  
Frederic Capel ◽  
Anne Tournadre
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Fatty Acids ◽  
Density Lipoprotein ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Cvd Risk ◽  
Cardiometabolic Diseases ◽  
Increased Risk ◽  
Muscle Health

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a high prevalence of death due to cardiometabolic diseases. As observed during the aging process, several comorbidities, such as cardiovascular disorders (CVD), insulin resistance, metabolic syndrome and sarcopenia, are frequently associated to RA. These abnormalities could be closely linked to alterations in lipid metabolism. Indeed, RA patients exhibit a lipid paradox, defined by reduced levels of total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol whereas the CVD risk is increased. Moreover, the accumulation of toxic lipid mediators (i.e., lipotoxicity) in skeletal muscles can induce mitochondrial dysfunctions and insulin resistance, which are both crucial determinants of CVD and sarcopenia. The prevention or reversion of these biological perturbations in RA patients could contribute to the maintenance of muscle health and thus be protective against the increased risk for cardiometabolic diseases, dysmobility and mortality. Yet, several studies have shown that omega 3 fatty acids (FA) could prevent the development of RA, improve muscle metabolism and limit muscle atrophy in obese and insulin-resistant subjects. Thereby, dietary supplementation with omega 3 FA should be a promising strategy to counteract muscle lipotoxicity and for the prevention of comorbidities in RA patients.

scholarly journals Sex Difference Impacts on the Relationship between Paraoxonase-1 (PON1) and Type 2 Diabetes

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 683
Author(s):  
Valentina Rosta ◽  
Alessandro Trentini ◽  
Angelina Passaro ◽  
Giovanni Zuliani ◽  
Juana Maria Sanz ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Complications ◽  
Serum Glucose ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Partial Loss ◽  
The Relationship ◽  
Gender Specific

Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease. To address this aim, we assessed PON1 activity in the sera of 778 patients, including controls (women, n = 383; men, n = 198) and diabetics (women, n = 79; men = 118). PON1 activity decreased in both women and men with T2D compared with controls (p < 0.05 and p > 0.001, respectively), but the change was 50% larger in the female cohort. In line with this result, the enzyme activity was associated with serum glucose level only in women (r = −0.160, p = 0.002). Notably, only within this gender category, lower PON1 activity was independently associated with increased odds of being diabetic (odds ratio (95% Confidence interval: 2.162 (1.075–5.678)). In conclusion, our study suggests that PON1-deficiency in T2D is a gender-specific phenomenon, with women being more affected than men. This could contribute to the partial loss of female cardiovascular advantage associated with T2D.

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