scholarly journals The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2872
Author(s):  
Hassan T. Aboufarrag ◽  
Paul W. Needs ◽  
Gerald Rimbach ◽  
Paul A. Kroon
Keyword(s):  
Gene Expression ◽  
Enzyme Activities ◽  
Molecular Mechanisms ◽  
Oxidized Ldl ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Microbial Metabolites ◽  
Hdl Function ◽  
Pon1 Gene ◽  
Gene Assay

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (−22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.

scholarly journals Regulation of Hepatic Paraoxonase-1 Expression

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Bianca Fuhrman
Keyword(s):  
Gene Expression ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Atherosclerotic Lesions ◽  
Pon1 Gene ◽  
Increased Risk ◽  
Primary Determinant ◽  
Artery Disease ◽  
Atherosclerosis Development ◽  
Serum Paraoxonase

Serum paraoxonase-1 (PON1) is a member of the paraoxonases family (PON1, PON2, and PON3). PON1 is synthesized and secreted by the liver, and in circulation it is associated with HDL. PON1 has antioxidative properties, which are associated with the enzyme’s capability to decrease oxidative stress in atherosclerotic lesions and to attenuate atherosclerosis development. Epidemiological evidence demonstrates that low PON1 activity is associated with increased risk of cardiovascular events and cardiovascular disease and is an independent risk factor for coronary artery disease. Therefore, pharmacological modulation of PON1 activity or PON1 gene expression could constitute a useful approach for preventing atherosclerosis. A primary determinant of serum PON1 levels is the availability of the enzyme for release by the liver, the principal site of PON1 production. Together with the enzyme secretion rate, enzymatic turnover, and protein stability, the level of PON1 gene expression is a major determinant of PON1 status. This paper summarizes recent progress in understanding the regulation of PON1 expression in hepatocytes.

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

VASA ◽  
2017 ◽  
Vol 46 (5) ◽  
pp. 370-376 ◽  
Author(s):  
Anita Szentpéteri ◽  
Noémi Zsíros ◽  
Viktória E. Varga ◽  
Hajnalka Lőrincz ◽  
Mónika Katkó ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Oxidized Ldl ◽  
Vascular Complications ◽  
Cd40 Ligand ◽  
Paraoxonase 1 ◽  
Intercellular Adhesion Molecule ◽  
Pon1 Activity ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Parameters ◽  
Vascular Biomarkers

Abstract. Background: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. Patients and methods: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. Results: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. Conclusions: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

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.

PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease

2018 ◽  
Vol 71 (11) ◽  
pp. 963-970
Author(s):  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
Dunja Rogić ◽  
Ivana Rako ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Operating Characteristic ◽  
Fragment Length Polymorphism ◽  
Characteristic Curve ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Pon1 Gene

AimsChronic obstructive pulmonary disease (COPD) is characterised with oxidative stress. Paraoxonase 1 (PON1) is an enzyme, coded by PON1 gene, with distinctive antiatherogenic and antioxidative roles. We aimed to investigate the frequencies of Q192R, L55M and −108C>T polymorphisms and association of those polymorphisms with paraoxonase and arylesterase activities in patients with COPD.MethodsPON1 genotype was determined by PCR–restriction fragment length polymorphism method. PON1 activity was measured by paraoxon and phenylacetate.ResultsOnly −108C>T polymorphism resulted in significantly different distribution of genotypes and alleles, with higher frequency of TT genotype and T allele in patients compared with control subjects. Moreover, T allele (OR 2.29 (95% CI 1.54 to 3.41); p<0.001) as well as TT genotype (OR 5.00 (95% CI 2.19 to 11.43); p<0.001) showed an association with the disease. −108C>T polymorphism was suggested as a significant diagnostic predictor for the disease (OR (95% CI) 2.65 (1.53 to 4.59), p=0.001), with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84 to 0.93) and with 83.90% of correctly classified cases.ConclusionsHigher frequency of TT genotype and T allele could contribute to the observed reduction of PON1 activity in patients with COPD. T allele and TT genotype are associated with COPD, and the PON1−108C>T polymorphism could be a potential predictor of the disease.

scholarly journals Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Preserves HDL Atheroprotective Functions

2019 ◽  
Author(s):  
Jiansheng Huang ◽  
Patricia G. Yancey ◽  
Huan Tao ◽  
Mark Borja ◽  
Loren Smith ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Adduct Formation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Dependent Manner ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Impaired Ability ◽  
Anti Inflammatory ◽  
Mediated Oxidation

AbstractHigh-density lipoprotein (HDL) is atheroprotective by mediating cholesterol efflux, anti-inflammatory, and anti-oxidation functions. Atheroprotective functions of HDL are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished and MDA-HDL adduct levels were decreased. In addition, PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from Apoe-/- macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity in a dose dependent manner. In addition, MDA modification of HDL reduced its anti-inflammatory function compared to native HDL as the expression of IL-1β and IL6 increased by 3-(p<0.05) and 1.8-fold (p<0.05) in Apoe-/- macrophages in response to LPS. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and normalization of the PON1 activity to PON1 mass revealed a 24 % (p<0.05) decrease in specific activity indicating that PON1 activity is also impaired in FH. Consistent with the impaired PON1 activity and increased MDA-apoAI, FH-HDL induced a pro-inflammatory response in Apoe-/- macrophages compared to incubation with LPS alone. FH-HDL versus control HDL also had an impaired ability to promote cholesterol efflux from Apoe-/- macrophages. Interestingly, reactive dicarbonyl scavengers effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Importantly, in vivo treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers effectively reduced MDA-HDL adduct formation and increased PON1 activity and HDL cholesterol efflux capacity, supporting a therapeutic potential of reactive carbonyl scavenging in maintaining HDL function.

scholarly journals Effects of Intronic and Exonic Polymorphisms of Paraoxonase 1 (PON1) Gene on Serum PON1 Activity in a Korean Population

2011 ◽  
Vol 26 (6) ◽  
pp. 720 ◽  
Author(s):  
Sang-Yong Eom ◽  
Yun-Sik Kim ◽  
Chung-Jong Lee ◽  
Chul-Ho Lee ◽  
Yong-Dae Kim ◽  
...  
Keyword(s):  
Korean Population ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Pon1 Gene ◽  
Serum Pon1 Activity

scholarly journals Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

2008 ◽  
Vol 50 (4) ◽  
pp. 223-227 ◽  
Author(s):  
Elaine Nunes Daminelli ◽  
Celso Spada ◽  
Arício Treitinger ◽  
Tatiane Vanessa Oliveira ◽  
Maria da Conceição Latrilha ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Premature Coronary Artery Disease ◽  
Cholesteryl Esters ◽  
Hiv Patients ◽  
Hdl Function

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

scholarly journals Expression of Exogenous Sam68, the 68-Kilodalton Src-Associated Protein in Mitosis, Is Able To Alleviate Impaired Rev Function in Astrocytes

2002 ◽  
Vol 76 (9) ◽  
pp. 4526-4535 ◽  
Author(s):  
Jinliang Li ◽  
Ying Liu ◽  
In-Woo Park ◽  
Johnny J. He
Keyword(s):  
Gene Expression ◽  
Nuclear Export ◽  
Molecular Mechanisms ◽  
Subcellular Fractionation ◽  
Dominant Negative ◽  
Double Mutation ◽  
Gene Assay ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) gene expression in astrocytes is restricted, resulting in a brief and limited synthesis of HIV-1 viral structural proteins. Impaired Rev function has been documented in these cells. However, the molecular mechanisms underlying the impaired Rev function are not fully understood. Using the astroglial cell line U87.MG as a model, we report here that HIV-1 gene expression down-regulated expression of Sam68, the 68-kDa Src-associated protein in mitosis, which was constitutively expressed at a lower level in astrocytes. Elevating the endogenous level of Sam68 expression considerably restored HIV-1 Rev function in astrocytes, as determined by a Rev-dependent reporter gene assay. However, elevation of Sam68 expression achieved only a modest increase in HIV-1 production, further supporting the notion that there are multiple cellular restrictions of HIV-1 gene expression in astrocytes. Mutagenesis analysis identified the region between amino acids 321 and 410 of Sam68 as being directly involved in the binding of Sam68 to Rev, while a double mutation in Rev, L78D and E79L, like those in the dominant-negative Rev mutant M10, eliminated Rev binding to Sam68. Moreover, subcellular fractionation and digital fluorescence microscopic imaging revealed that Sam68 expression promoted Rev nuclear export. Taken together, our studies demonstrate that a lower level of constitutive Sam68 expression, followed by further down-regulation by HIV-1 infection, contributes to impaired Rev function in astrocytes, and they suggest that Sam68 may play an important role in Rev nuclear export.

scholarly journals The effect of paraoxonase 1 (PON1) gene polymorphisms T(-107)C and L55M and diet composition on serum PON1 activity in women

2021 ◽  
Author(s):  
Bianka Machado Zanini ◽  
Leticia Burkert ◽  
Fabiola Goettem dos Santos ◽  
Michal M. Masternak ◽  
José Augusto Crespo-Ribeiro ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Diet Composition ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Pon1 Gene ◽  
Serum Pon1 Activity

scholarly journals Implication of Low HDL-c Levels in Patients with Average LDL-c Levels: A Focus on Oxidized LDL, Large HDL Subpopulation, and Adiponectin

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Filipa Mascarenhas-Melo ◽  
José Sereno ◽  
Edite Teixeira-Lemos ◽  
Daniela Marado ◽  
Filipe Palavra ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Serum Glucose ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Low Hdl ◽  
The Impact

To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n=169) and control subjects (n=73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF-α, adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients’ subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients’ subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

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