scholarly journals 3-D Structure of Serum Paraoxonase 1 Sheds Light on Its Activity, Stability, Solubility and Crystallizability

2007 ◽  
Vol 58 (3) ◽  
pp. 347-353 ◽  
Author(s):  
Michal Harel ◽  
Boris Brumshtein ◽  
Ran Meged ◽  
Hay Dvir ◽  
Raimond Ravelli ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Activity ◽  
High Density Lipoprotein ◽  
Active Site ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Hydrolytic Activities ◽  
Wide Range ◽  
The Stability ◽  
Serum Paraoxonase

3-D Structure of Serum Paraoxonase 1 Sheds Light on Its Activity, Stability, Solubility and CrystallizabilitySerum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases. PON1 and PON3 reside on high-density lipoprotein (HDL) (the "good cholesterol"), and are involved in the alleviation of atherosclerosis. Members of the PON family have been identified not only in mammals and other vertebrates, but also in invertebrates. We earlier described the first crystal structure of a PON family member, a directly-evolved variant of PON1, at 2.2 Å resolution. PON1 is a 6-bladed beta-propeller with a unique active-site lid which is also involved in binding to HDL. The 3-D structure, taken together with directed evolution studies, permitted analysis of mutations which enhanced the stability, solubility and crystallizability of this PON1 variant. The structure permits a detailed description of PON1's active site and suggests possible mechanisms for its catalytic activity on certain substrates.

Catalytic Stimulation by Restrained Active-Site Floppiness—The Case of High Density Lipoprotein-Bound Serum Paraoxonase-1

2015 ◽  
Vol 427 (6) ◽  
pp. 1359-1374 ◽  
Author(s):  
Moshe Ben-David ◽  
Joel L. Sussman ◽  
Christopher I. Maxwell ◽  
Klaudia Szeler ◽  
Shina C.L. Kamerlin ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Active Site ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
Serum Paraoxonase

scholarly journals Distribution of paraoxonase 1 coding region polymorphisms in Serbian population

Genetika ◽  
2010 ◽  
Vol 42 (2) ◽  
pp. 235-247 ◽  
Author(s):  
I. Pejin-Grubisa ◽  
I. Buzadzic ◽  
B. Jankovic-Orescanin ◽  
N. Barjaktarovic-Vucinic
Keyword(s):  
Catalytic Activity ◽  
High Density Lipoprotein ◽  
Organophosphorus Pesticides ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Coding Region ◽  
Pon1 Gene ◽  
Toxic Metabolites ◽  
Gene Coding ◽  
Serum Paraoxonase

Serum paraoxonase 1 (PON1) in humans is a protein component of high-density lipoprotein (HDL) particles that protects against oxidative damage, detoxifies toxic metabolites of organophosphorus pesticides and nerve agents and activates or inactivates specific drugs. It has been reported that PON1 gene coding region polymorphisms, L55M and Q192R, could influence both expression level and catalytic activity of PON1, and their link with a broad spectrum of diseases has been described. The aim of this study was to determine the frequencies of PON1 coding region polymorphisms Q192R and L55M in Serbian population. The most frequent alleles were Q (0.77) for Q192R and L (0.68) for L55M. Genotypes QQ (0.60) and LL (0.47) and combined genotype QQ/LL (0.26) were the most frequent in examined population.

MiR-145-5p modulates lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia

2021 ◽  
pp. 1-7
Author(s):  
Huijun Chen ◽  
Jing Gao ◽  
Qian Xu ◽  
Dongmei Wan ◽  
Wenji Zhai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Density Lipoprotein ◽  
Macrophage Polarization ◽  
Density Lipoprotein ◽  
High Density ◽  
M2 Macrophage ◽  
Cardiac Tissues ◽  
Potential Biomarker ◽  
Wide Range ◽  
M2 Macrophage Polarization

The present study aims to explore the role of microRNA 145-5p (miR-145-5p) in hyperlipidemia. Using bioinformatics tools and a wide range of function and mechanism assays, we attempted to understand the specific function and potential mechanism of miR-145-5p in hyperlipidemia. A cholesterol-enriched diet induced an increase of serum cholesterol and triacylglycerol but a decrease of serum high-density lipoprotein. MiR-145-5p level was decreased in hyperlipidemia rat models. MiR-145-5p regulated lipid metabolism by antagonizing the alteration of high-density lipoprotein, cholesterol, and triacylglycerol in serum mediated by a cholesterol-enriched diet. In mechanism, miR-145-5p directly bound with p21 protein (RAC1)-activated kinase 7 (PAK7) and negatively regulated mRNA and protein levels of PAK7 in THP-1 cells. Furthermore, miR-145-5p level was negatively associated with PAK7 level in rat cardiac tissues. Finally, overexpression of PAK7 reversed the effects of miR-145-5p on β-catenin activation and M2 macrophages polarization in THP-1 cells. In conclusion, MiR-145-5p modulated lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia, which may provide a potential biomarker for the treatment of hyperlipidemia-induced cardiovascular diseases.

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 Altered Flow-Mediated Vasodilatation, Low Paraoxonase-1 Activity, and Abnormal High-Density Lipoprotein Subclass Distribution in Takayasu's Arteritis

2009 ◽  
Vol 73 (4) ◽  
pp. 760-766 ◽  
Author(s):  
Nilda Espinola-Zavaleta ◽  
María Elena Soto-López ◽  
Elizabeth Carreón-Torres ◽  
Ricardo Gamboa ◽  
Ana M. Mejía ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Takayasu’S Arteritis ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
Takayasu's Arteritis ◽  
Lipoprotein Subclass

scholarly journals Three routine methods for measuring high-density lipoprotein cholesterol compared with the Reference Method

1996 ◽  
Vol 42 (5) ◽  
pp. 738-743 ◽  
Author(s):  
N Harris ◽  
V Galpchian ◽  
N Rifai
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Dextran Sulfate ◽  
Direct Method ◽  
Density Lipoprotein ◽  
Reference Method ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Direct Assay ◽  
Wide Range

Abstract We compared the performance of three methods for quantifying high-density lipoprotein cholesterol (HDL-C) with the Reference Method for HDL-C, using samples with a wide range of triglyceride (TG) concentrations (290-18000 mg/L). All three comparison assays-- utilizing a magnetic dextran sulfate precipitating reagent, a direct method, and a standard MgCl2-dextran sulfate reagent--were precise, with a run-to-run CV of less than or equal to 4.1%. However, the systematic error of these assays exceeded the National Cholesterol Education Program (NCEP) performance goal of less than or equal to 10% in half of the concentration ranges tested. Nevertheless, the total error of the assays generally meets the current 22% limit set by the NCEP. Although both the magnetic dextran sulfate precipitation reagent and the direct assay can be performed more rapidly than the MgCl2-dextran sulfate assay, the direct assay involves no sample preparation and requires only 4 microL of sample excluding the dead space. Although precipitation is frequently inadequate with the MgCl2-dextran sulfate reagent at TG concentrations >6000 mg/L, both the magnetic and the direct reagent show no interference from high TG concentrations as great as 18 000 mg/L.

The association between lecithin–cholesterol acyltransferase activity and fatty liver index

2019 ◽  
Vol 56 (5) ◽  
pp. 583-592 ◽  
Author(s):  
Jelena Janac ◽  
Aleksandra Zeljkovic ◽  
Zorana Jelic-Ivanovic ◽  
Vesna Dimitrijevic-Sreckovic ◽  
Milica Miljkovic ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Fatty Liver ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
Acyltransferase Activity ◽  
Lecithin Cholesterol Acyltransferase ◽  
Liver Index ◽  
Fatty Liver Index

Background Non-alcoholic fatty liver disease is a frequent ailment with known complications, including those within the cardiovascular system. Associations between several indicators of high-density lipoprotein metabolism and function with clinical and laboratory parameters for the assessment of fatty liver index, a surrogate marker of non-alcoholic fatty liver disease, were evaluated. Methods The study comprised 130 patients classified according to fatty liver index values: fatty liver index < 30, fatty liver index 30–59 (the intermediate group) and fatty liver index ⩾ 60. Lecithin–cholesterol acyltransferase and cholesteryl ester transfer protein activities were determined. Paraoxonase 1 concentration and its activity, paraoxonase 3 concentration and high-density lipoprotein subclass distribution were assessed. Results Increased lecithin–cholesterol acyltransferase activity correlated with increased fatty liver index ( P < 0.001). Paraoxonase 3 concentration was lower in the fatty liver index ⩾ 60 group compared with the fatty liver index < 30 group ( P < 0.05). Cholesteryl ester transfer protein activity, paraoxonase 1 concentration and its activity did not significantly differ across the fatty liver index groups. The relative proportion of small-sized high-density lipoprotein 3 subclass was higher in the fatty liver index ⩾ 60 group compared with the other two fatty liver index groups ( P < 0.01). Lecithin–cholesterol acyltransferase activity positively associated with the fatty liver index ⩾ 60 group and remained significant after adjustment for other potential confounders. Only the triglyceride concentration remained significantly associated with lecithin–cholesterol acyltransferase activity when the parameters that constitute the fatty liver index equation were examined. Conclusions Higher lecithin–cholesterol acyltransferase activity is associated with elevated fatty liver index values. Significant independent association between triglycerides and lecithin–cholesterol acyltransferase activity might indicate a role of hypertriglyceridaemia in alterations of lecithin–cholesterol acyltransferase activity in individuals with elevated fatty liver index.

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