scholarly journals Species- and substrate-specific stimulation of human plasma paraoxonase 1 (PON1) activity by high chloride concentration.

2002 ◽  
Vol 49 (4) ◽  
pp. 927-936 ◽  
Author(s):  
Jerzy Bełtowski ◽  
Grazyna Wójcicka ◽  
Andrzej Marciniak
Keyword(s):  
Mammalian Species ◽  
Chloride Concentration ◽  
Plasma Lipoproteins ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Halide Anion ◽  
Plasma High Density ◽  
High Concentrations

Paraoxonase 1 (PON1), contained in plasma high-density lipoproteins, plays an important role in the protection of plasma lipoproteins and cell membranes from oxidative damage. Previous studies indicate that human PON1 is stimulated by high NaCl concentrations. The aim of this study was to characterize in more detail the effect of salts on serum PON1. Paraoxon-hydrolyzing activity of human serum was stimulated by 81.6% following the addition of 1 M NaCl. The effect of NaCl was dose-dependent between 0.5 and 2 M. PON1 activity toward phenyl acetate was reduced by 1 M NaCl by 55.2%. Both the paraoxon- and phenyl acetate-hydrolysing activity was slightly lower in heparinized plasma than in serum, but NaCl had similar stimulatory and inhibitory effects on these activities, respectively. In rat, rabbit, and mouse, NaCl reduced PON1 activity. KCl had a similar effect on human PON1 as NaCl. Sodium nitrite also stimulated human PON1 but much less effectively than chloride salts. In contrast, sucrose, sodium acetate and sodium lactate had no significant effect. NaBr was a less effective PON1 activator than NaCl, whereas the effect of NaJ was non-significant. The activity of human PON1 toward homogentisic acid lactone and gamma-decanolactone was unaltered by NaCl. These data indicate that: 1) high concentrations of chlorides stimulate human PON1 activity toward paraoxon but not other substrates, 2) PON1 is inhibited by Cl(-) in other mammalian species, 3) the potency of human PON1 activation by halogene salts increases with decreasing atomic mass of the halide anion.

Paraoxonase 1 activity in different types of multiple sclerosis

2009 ◽  
Vol 15 (3) ◽  
pp. 399-402 ◽  
Author(s):  
A Jamroz-Wisniewska ◽  
J Beltowski ◽  
Z Stelmasiak ◽  
H Bartosik-Psujek
Keyword(s):  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Control Group ◽  
Progressive Type ◽  
Relapsing Remitting ◽  
Different Types ◽  
Plasma High Density ◽  
The Brain

Background Paraoxonase 1 (PON1) is an antioxidant enzyme bound to plasma high-density lipoproteins and is also present in the brain. Objective The aim of this study was to estimate the activity of PON1 in patients with different types of MS. Methods The PON1 activity toward paraoxon and phenyl acetate and lipid profile was examined in 40 relapsing-remitting (RR) patients in relapse, in 42 RR patients in remission, in 55 progressive MS patients and in 40 healthy individuals. Results PON1 activity did not differ in MS patients compared to control group. PON1 activity in relapse was significantly lower in comparison to the other MS groups. Hypercholesterolemia was observed in MS patients. Conclusion PON1 activity does not change in the course of stable and progressive type of MS and is decreased by the relapse of MS.

LIPOPROTEIN BINDING TOHUMAN PLATELETS IS LOCATED AT GPIIb/IIIa COMPLEX

1987 ◽  
Author(s):  
E Koller ◽  
F Koller
Keyword(s):  
Specific Binding ◽  
Human Platelets ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Molecular Weights ◽  
Disulfide Reduction ◽  
Specific Binding Sites ◽  
First Results ◽  
Lipoprotein Binding ◽  
High Concentrations

Human Platelets possess specific binding sites for low density lipoproteins (LDL) and high density lipoproteins(HDL)(1). Binding of both classes of plasma lipoproteins, though competitive, has been shown by several groups to facilitate platelet activation.Isolated washed platelets occasionally aggregate upon addition of high concentrations of LDL even in the absence of known platelet activators. The proteins responsible for this binding have been visualized by ligand blotting (2). Both types of ligand specifically bind to two glycoproteins with molecular weights of 135 and 115 kD, respectively. The conditions of binding to these two proteins, however, markedly differ from those known for other lipoprotein receptors.Following extensive purification, these two species are still present at concentrations relative to each other that depend markedly on the conditions of purification. The purified, solubilized receptor was tested under various conditions, including in the absence and presence of calcium, after disulfide-reduction, and following chymotrypsin digestion. In parallel experiments, the same preparations were tested with respect to binding of fibrinogen, different lectins, and thealloantibody anti-PlAI . The results strongly support the assumption, that the two protein bands associated with lipoprotein binding are constituents of the GP-IIb/IIIa complex.These first results may have greatimplications for our understanding ofthe mechanism by which lipoproteins facilitate platelet stimulation.

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.

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.

Deficit schizophrenia and its features are associated with PON1 Q192R genotypes and lowered paraoxonase 1 (PON1) enzymatic activity: effects on bacterial translocation

CNS Spectrums ◽  
2020 ◽  
pp. 1-10 ◽  
Author(s):  
Andressa K. Matsumoto ◽  
Michael Maes ◽  
Thitiporn Supasitthumrong ◽  
Annabel Maes ◽  
Ana P. Michelin ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Immunoglobulin A ◽  
Quorum Quenching ◽  
Psychomotor Retardation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Gram Negative ◽  
Deficit Schizophrenia ◽  
Thought Disorders

Abstract Background. Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods. In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured. Results. DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions. The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

scholarly journals Paraoxonase-1 and Simvastatin Treatment in Patients with Stable Coronary Artery Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Rafał Januszek
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Control Group ◽  
Simvastatin Treatment ◽  
Simvastatin Therapy ◽  
Artery Disease

Background.Paraoxonase-1 (PON1) is the crucial antioxidant marker of high-density lipoproteins. The present study is aimed at assessing the effect of simvastatin treatment on PON1 activity and its relationship to Q192R and M55L polymorphisms in subjects with stable coronary artery disease (CAD).Methods.The patient group was composed of 53 individuals with stable CAD, and the control group included 53 sex-matched police officers without CAD. CAD patients were treated with simvastatin 40mg/day for 12 months. Respectively, flow mediated dilatation (FMD), serum hs-CRP and TNF-αlevels, urinary 8-iso-PGF2αconcentrations, and PON1 activity were evaluated in definitive intervals.Results.There was no effect of simvastatin treatment on urinary 8-iso-PGF2α. Simvastatin treatment significantly increased FMD value, decreased CRP and TNF-αconcentration. After adjusting for PON1 genotypes, significantly higher PON1 activity was noted in the 192R allele carriers, in both groups. Regardless of genotype, PON1 activity remained stable after simvastatin treatment.Conclusions.The present study confirms a positive effect of simvastatin therapy on endothelial function and inflammatory markers in secondary prevention. Simvastatin treatment shows no effects on PON1 activity and 8-isoprostanes level. The effect of simvastatin therapy on PON1 activity is not modulated by Q192R and M55L polymorphisms.

scholarly journals In Schizophrenia, PON1 Q192R Genotypes and/or Lowered Paraoxonase 1 (PON1) Enzymatic Activity are Significantly Associated with the Deficit Syndrome, Negative Symptoms, Formal Thought Disorders, Psychomotor Retardation, Excitation and Increased IgA Levels to Gram-Negative Microbiota

2019 ◽  
Author(s):  
Andressa Keiko Matsumoto ◽  
Michael Maes ◽  
Annabel Maes ◽  
Ana Paula Michelin ◽  
Laura de Oliveira Semeão ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Quorum Quenching ◽  
Psychomotor Retardation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Gram Negative ◽  
Deficit Syndrome ◽  
Deficit Schizophrenia ◽  
Thought Disorders

Background: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods: In this case-control study, Thai women and men, aged 18-65 years, were divided in DS (n=40) and NDS (n=40) and were compared to controls (n=40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and IgA levels responses directed to Gram-negative bacteria were measured. Results: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

scholarly journals The effects of insulin deficiency on the plasma clearance and exchange of high-density-lipoprotein phosphatidylcholine in rats

1992 ◽  
Vol 281 (3) ◽  
pp. 851-857 ◽  
Author(s):  
I J Martins ◽  
T G Redgrave
Keyword(s):  
Plasma Clearance ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Cholesteryl Oleate ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Phospholipid Transfer ◽  
Plasma High Density

Triolein/cholesteryl oleate/cholesterol/phosphatidylcholine emulsions designed to model the lipid composition of chylomicrons were injected intravenously into control and streptozotocin-treated insulin-deficient rats. As previously described for lymph chylomicrons, the emulsion triolein was hydrolysed and phosphatidylcholine was transferred to the plasma high-density lipoproteins (HDL). This mechanism was used to introduce a phospholipid label into HDL in vivo. The subsequent clearance of phospholipid radioactivity from the plasma of insulin-deficient rats was significantly slower than in controls (P less than 0.025). Plasma clearance was similarly slower in insulin-deficient rats after injection of HDL that was previously labelled with radioactive phospholipids. After injection, the phospholipid label redistributed rapidly between the large-particle fraction of plasma lipoproteins (very-low- and low-density lipoproteins), and the lighter and heavier fractions of HDL. Compared with control rats, in insulin-deficient rats less of the phospholipid label was distributed to the lighter HDL fraction and more to the heavier HDL fraction, and this difference was not due to changes in activity of lecithin: cholesterol acyltransferase or in the apparent activity of phospholipid transfer protein. In insulin-deficient rats the changes in HDL phospholipid clearance and exchange appeared to be secondary to the associated hypertriglyceridaemia and the related changes in distribution of phospholipids between classes of plasma lipoproteins.

scholarly journals Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery

2019 ◽  
Vol 8 (4) ◽  
pp. 441 ◽  
Author(s):  
Anna Wysocka ◽  
Marek Cybulski ◽  
Andrzej P.Wysokiński ◽  
Henryk Berbeć ◽  
Janusz Stążka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Family History ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Diabetic Patients ◽  
Paraoxonase Activity

Background: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. Materials and methods: Investigated population consisted of 71 patients aged 43–76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for –108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR–RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. Results: Significant correlations between diabetes mellitus and paraoxonase activity (R = –0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = –0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. Conclusions: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.

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