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PON1 Activity (pon1 + activity)

Distribution by Scientific Domains

Medical Sciences	58%
Life Sciences	33%

Selected Abstracts

Quercetin and Ethanol Attenuate the Progression of Atherosclerotic Plaques With Concomitant Up Regulation of Paraoxonase1 (PON1) Gene Expression and PON1 Activity in LDLR,/, Mice

ALCOHOLISM, Issue 9 2010
Leslie C. Leckey
Background:, As moderate wine drinking is atheroprotective, it is clinically relevant to elucidate its possible mechanism/s of action/s. Our objective is to demonstrate the potential benefits of the wine components, quercetin and ethanol, on the development of aortic plaques with parallel changes in antiatherogenic factors. Methods and Results:, The effects of quercetin and ethanol on the development of aortic atherosclerotic lesions, liver PON1 gene expression, and serum PON1 activity were measured in LDLR,/, mice on an atherogenic diet for 4 and 8 weeks. Depending on the duration and dosage of these modulators, 12.5 to 25 mg/dl quercetin (12.5Q to 25Q) and 18 to 25% ethanol, the magnitude of decreases in aortic lesions caused by moderate ethanol and quercetin ranged from 20 to 70% (p < 0.05 to p < 0.001) based on ultrasound biomicroscopy (UBM) analyses, and from 18 to 61% (p < 0.05 to p < 0.001) based on morphometric analyses. The composite plot of all the UBM and morphometric data showed significant correlation between these 2 methods (p = 0.0001, Pearson r = 0.79 for 4-week treatment; p = 0.000004, Pearson r = 0.84 for 8-week treatment). Concomitantly, 4-week treatments with 12.5Q and 18% ethanol up regulated liver PON1 mRNA by 41% (p < 0.05) and 37% (p < 0.05), respectively, accompanied by 92% (p < 0.001) and 61% (p < 0.001) increases in serum PON1 activity, respectively. The corresponding values after 8-week treatment with 12.5Q and 18% ethanol were 23% (p < 0.05) and 40% (p < 0.02) with respect to the up regulation of liver PON1 mRNA expression, while the stimulations of serum PON1 activity were 75% (p < 0.001) and 90% (p < 0.001), respectively. Conclusions:, Based on these findings, we conclude that quercetin and moderate ethanol significantly inhibit the progression of atherosclerosis by up regulating the hepatic expression of the antiatherogenic gene, PON1, with concomitant increased serum PON1 activity. [source]

Genetic Variation in the Paraoxonase-3 (PON3) Gene is Associated with Serum PON1 Activity

ANNALS OF HUMAN GENETICS, Issue 1 2008
Dharambir K. Sanghera
Summary Low serum paraoxonase1 (PON1) activity determined by paraoxon substrate is associated with coronary heart disease (CHD), diabetes and systemic lupus erythematosus (SLE) risk. In this investigation, we have examined the role of genetic variation in the PON3 gene in relation to PON1 activity and SLE risk in a biracial sample comprising 377 SLE patients and 482 controls from US whites and blacks. We genotyped six PON3 tagging single nucleotide polymorphisms (tagSNPs) and examined their associations with PON1 activity, SLE risk, antiphopholipid autoantibodies (APA), lupus nephritis, carotid vascular disease, and inflammation. With the exception of PON1 activity, no other significant associations were found with PON3 SNPs. Multiple regression analysis including all six PON3 tagSNPs and PON1/Q192R and L55M SNPs revealed significant association of PON1 activity with 4 SNPs: PON3/A10340C (p < 0.0001), PON3/A2115T (p = 0.002), PON1/L55M (p < 0.0001) and PON1/Q192R (p < 0.0001). These four SNPs explained 2%, 1%, 8% and 19% of the variation in PON1 activity, respectively. In summary, our new data indicate that genetic variation in the PON3 gene influences serum PON1 activity independently of the known effect of PON1 genetic variation. To our knowledge, this is the first study reporting the association of the PON3 gene variants with PON1 activity. [source]

Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2002
B. Mackness
Abstract Background The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. Design Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. Results Both PON1 activity and concentration were significantly lower by 16·7% and 19·2% (both P < 0·05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. Conclusions Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established. [source]

Paraoxonase activity in two healthy populations with differing rates of coronary heart disease

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2000
Mackness
Background The rate of coronary heart disease is over three-fold greater in Belfast than in Toulouse and the excess risk cannot be totally explained by ,classical' risk factors such as total cholesterol, LDL-cholesterol, smoking, etc. Design The effect of the human serum paraoxonase (PON1) 192-genetic polymorphism on plasma lipid and lipoprotein concentrations and on PON1 activity and concentration was investigated in 186 randomly selected healthy subjects from Toulouse and 165 from Belfast. Results The frequency of the R allele of PON1, which has been related to the risk of coronary heart disease, was significantly higher in Belfast (0.33) than in Toulouse (0.24; ,2 = 7.229, P = 0.0072). Subjects from Belfast also had significantly higher serum cholesterol, triglycerides, LDL-cholesterol, and apolipoprotein B, and significantly lower HDL-cholesterol and apolipoprotein A1, but these lipoprotein parameters were independent of the PON1 192-polymorphisms. PON1 activity towards paraoxon was significantly higher in the Belfast population than in Toulouse (median values: 179.7 vs. 129.4 nmol min,1 mL,1 serum, respectively; P < 0.05), which is consistent with our finding of a greater prevalence of the R allele. The median serum concentration of PON1 was 56.3 ,g mL,1 in Belfast, which was significantly lower (P < 0.005) than the level of 71 ,g mL,1 in Toulouse. Conclusions Our results thus provide further support for the hypothesis that populations at increased CHD risk have diminished serum PON1 concentration and an increased prevalence of the R allele of PON1. They are also consistent with reports that the ability of PON1 to hydrolyse paraoxon is inversely related to its capacity to hydrolyse lipid-peroxides, and thus to its antiatherogenic action. [source]

Paraoxonase-1 (PON1) activity as a risk factor for atherosclerosis in chronic renal failure patients

HEMODIALYSIS INTERNATIONAL, Issue 4 2008
Saeed Abdelwhab SAEED
Abstract Paraoxonase is a high-density lipoprotein-associated enzyme and has been shown to reduce the susceptibility to low-density lipoprotein peroxidation. This study aimed to investigate the activity of serum paraoxonase in uremic patients on hemodialysis (HD) and in the predialysis period, and to evaluate the correlations of vascular disease with paraoxonase activity. Thirty patients with chronic renal failure (CRF) undergoing HD (group 1), 30 patients with CRF under conservative treatment (group 2), and 30 healthy controls (group 3) were included. Basal, salt-stimulated, and arylesterase activity were tested by UV spectrophotometry. Serum lipid parameters were determined. B-Mode Doppler ultrasound was used to assess common carotid intima-media thickness (IMT). Basal paraoxonase, salt-stimulated, and arylesterase activity showed no significant difference between group 1 and group 2. However, it was significantly lower in group 1 and in group 2 than controls. Carotid IMT was significantly higher in group 1 than group 2 and both were significantly higher than controls. Basal paraoxonase-1 (PON1), salt-stimulated PON1, and arylesterase activity correlate with BUN, but only basal PON1 and salt-stimulated PON1 correlate with serum albumin. Linear regression showed that the most significant determinant of carotid IMT was PON1 arylesterase activity in group 1 and arylesterase activity and basal PON1 activity in group 2. Patients with CRF, whether under HD or conservative treatment, have reduced basal and stimulated paraoxonase activities, and this could be an important factor causing increased vascular disease in those patients. Modifying this factor can be of great value to protect against this common complication. [source]

The active site of human paraoxonase (PON1)

JOURNAL OF APPLIED TOXICOLOGY, Issue S1 2001
Denis Josse
Abstract Ideally we would like to treat people exposed to nerve agents with an enzyme that rapidly destroys nerve agents. The enzymes considered for such a role include human butyrylcholinesterase (BChE), acetylcholinesterase (AChE), carboxylesterase and paraoxonase (PON1). Success has been achieved in endowing BChE with the ability to hydrolyze organophosphates. The G117H mutant of BCHE hydrolyzes sarin and VX, whereas the double mutant G117H/E197Q hydrolyzes soman (Millard et al. Biochemistry 1995; 34: 15925,15933; 1998; 37: 237,247). However, the rates of organophosphate hydrolysis are slow and a faster organophosphate hydrolase is being sought. Native PON1 hydrolyzes paraoxon with a catalytic efficiency, of 2.4 × 106M,1min,1, and our goal is to improve the organophosphate hydrolase activity of PON1. To achieve this we need to identify the amino acids in the active site of PON1. Using site-directed mutagenesis and expression in human 293T cells, we have identified the following eight amino acids as being essential to PON1 activity: W280, H114, H133, H154, H242, H284, E52 and D53. Fluorescence of PON1 complexed to terbium ion shows that at least one tryptophan is close to the calcium binding site. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Quercetin and Ethanol Attenuate the Progression of Atherosclerotic Plaques With Concomitant Up Regulation of Paraoxonase1 (PON1) Gene Expression and PON1 Activity in LDLR,/, Mice

Betaine Protects Chronic Alcohol and ,-3 PUFA-Mediated Down-Regulations of PON1 Gene, Serum PON1 and Homocysteine Thiolactonase Activities With Restoration of Liver GSH

ALCOHOLISM, Issue 3 2010
Ravi Varatharajalu
Background:, Paraoxonase (PON1) is an antioxidant enzyme that prevents LDL oxidation as well as detoxifies homocysteine thiolactone (HCTL), both of which can cause atherosclerosis. Chronic alcohol (ETOH) and high ,-3 polyunsaturated fatty acids (,-3 PUFA) consumption may affect PON1 status presumably via reactive oxygen species by depleting liver glutathione (GSH), whereas betaine may counter their effects. Therefore, we investigated the influence of ETOH, ,-3 PUFA, and betaine on liver GSH, PON1 expression, lipid score, as well as serum PON1 and HCTLase activities. Methods:, Experimental rats belonging to various dietary groups were pair-fed with Lieber-DeCarli low (2.8% the dietary calories as ,3-fatty acids) and high (13.8% the dietary calories as ,3-fatty acids) menhaden fish alcohol-liquid diets with and without betaine (10 g/l diet) for 8 weeks after which liver PON1 mRNA, GSH, lipid score, and serum PON1, HCTLase, and ALT activities were measured. Results:, High ,-3 PUFA decreased liver PON1 mRNA expression, serum PON1, and HCTLase activity by 23% (p < 0.01), 20% (p < 0.05), and 28% (p < 0.05), respectively compared to the low ,-3 PUFA group. ETOH decreased PON1 mRNA expression by 25 and 30% (p < 0.01) with concomitant 27% (p < 0.05) and 38% (p < 0.01), decrease in liver GSH levels in low and high ,-3 PUFA groups, respectively. Correspondingly, serum PON1 activity decreased by 23% (p < 0.05) and 58% (p < 0.01) while serum HCTLase activity decreased by 25% (p < 0.05) and 59% (p < 0.01) in the low and high ,-3 PUFA ETOH groups, respectively. Betaine restored liver PON1 mRNA expressions in low and high ,-3 PUFA ETOH groups with parallel restorations of PON1 activity and liver GSH. Concomitantly, betaine reduced hepatosteatosis accompanied by alleviation of liver injury caused by chronic alcohol and high ,-3 PUFA. Conclusions:, Based on these results, we conclude that dietary betaine not only atheroprotective by restoring liver GSH that quenches free radicals, but also may alleviate liver injury by reducing hepatosteatosis. [source]

Genetic Variation in the Paraoxonase-3 (PON3) Gene is Associated with Serum PON1 Activity

Paraoxonases role in the prevention of cardiovascular diseases

BIOFACTORS, Issue 1 2009
Mira Rosenblat
Abstract Increased oxidative stress is a characteristic of patients with high risk for atherosclerosis development (hypercholesterolemic, hypertensive, diabetic), and the above phenomenon was shown to be associated with attenuated antioxidative status. The increased oxidative stress in atherosclerotic patients is present in their blood, as well as in their arterial wall cells, including macrophages, the hallmark of foam cells formation during early atherogenesis. Serum high density lipoprotein (HDL)-associated paraoxonase 1 (PON1) reduces oxidative stress in lipoproteins, in macrophages, and in the atherosclerotic lesion, whereas paraoxonase 2 (PON2, which is present in tissues, but not in serum) acts as an antioxidant at the cellular and not humoral level. Both PON1 and PON2 protect against atherosclerosis development, and this phenomenon could be related to their antioxidative properties. The use of nutritional antioxidants such as vitamin E, carotenoids (lycopene and ,-carotene), and mainly polyphenols (such as those present in red wine, licorice root ethanolic extract, or in pomegranate) by atherosclerotic animals and also by cardiovascular patients, leads to a reduction in oxidative stress and to the attenuation of atherosclerosis development. These latter phenomena could be related to the nutritional antioxidants-induced increase in HDL PON1 activity (effects on gene expression, on preventing enzyme inactivation, and on increasing PON1 stability through its binding to HDL), as well as an increase in macrophage PON2 activation (at the gene expression level). © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]