Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer's Disease.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer's disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no or gene expression. In the present study, we examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD.

Unexpectedly higher diazoxon hydrolysis by serum paraoxonase-1 in coronary heart disease.

Objectives: Low serum PON1 activities (paraoxon, phenyl-acetate or lactone substrates) are associated with coronary heart disease (CHD). We investigated the rate of diazoxon hydrolysis by PON1 in a population with CHD.

Design & Methods: Case- control study of 410 subjects with CHD and 274 controls.

Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles.

Human PON1 is a HDL-associated lipolactonase capable of preventing LDL and cell membrane oxidation and is therefore considered to be atheroprotective. PON1 contributes to the antioxidative function of HDL and reductions in HDL-PON1 activity, prevalent in a wide variety of diseases with an inflammatory component, are believed to lead to dysfunctional HDL which can promote inflammation and atherosclerosis. However, PON1 is multifunctional and may contribute to other HDL functions such as in innate immunity, preventing infection by quorum sensing gram negative bacteria by destroying acyl lactone mediators of quorum sensing, and putative new roles in cancer development and the promotion of healthy ageing.

Impaired paraoxonase-1 status in obese children. Relationships with insulin resistance and metabolic syndrome.

Objectives: To investigate the relationships between serum paraoxonase-1 (PON1), insulin resistance, and metabolic syndrome (MetS) in childhood obesity.

Design And Methods: We studied 110 obese children and 36 non-obese children with a similar gender and age distribution. We measured serum PON1 activity against 5-thiobutyl butyrolactone (TBBLase) and against paraoxon (paraoxonase).

Paraoxonase-1 is associated with corneal endothelial cell alterations in patients with chronic obstructive pulmonary disease.

Purpose: To investigate the relationships between the levels of the antioxidant enzyme paraoxonase-1 (PON1) and corneal endothelial alterations in patients with chronic obstructive pulmonary disease (COPD) undergoing cataract surgery.

Methods: We studied 172 patients with cataract attending our ophthalmology clinic. Based on spirometric analysis, they were segregated into two groups, 110 (64%) with COPD and 62 (36%) without COPD.

Paraoxonase-1 inhibits oxidized low-density lipoprotein-induced metabolic alterations and apoptosis in endothelial cells: a nondirected metabolomic study.

We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL.

Targeting paraoxonase-1 in atherosclerosis.

Introduction: Paraoxonase-1 (PON1) is a Ca(2+) dependent, high-density lipoprotein-associated lactonase which is capable of retarding/inhibiting low-density lipoprotein (LDL) oxidation. LDL oxidation is believed to be central to the initiation and progression of atherosclerosis, therefore, PON1 is considered to be atheroprotective.

Areas Covered: Relevant literature on PON1 was identified in PubMed.

Paraoxonase-1 (PON1) promoter region polymorphisms, serum PON1 status and coronary heart disease.

Introduction: Serum paraoxonase-1 (PON1) retards the oxidation of low-density lipoprotein and cell membranes and is atheroprotective. Polymorphisms in the promoter region of the PON1 gene have been shown to affect serum PON1 levels and have been related to the presence of coronary heart disease (CHD) in some studies. However, contradictory results have been reported with regard to promoter region polymorphisms and CHD presence; therefore we have re-examined the effects of the C-108T and G-909C promoter polymorphisms on PON1 levels and the presence of CHD in a large case-control study.

Paraoxonase-1 status in patients with hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1) is an enzyme that degrades lipid peroxides.

Paraoxonase-1 deficiency is associated with severe liver steatosis in mice fed a high-fat high-cholesterol diet: a metabolomic approach.

Oxidative stress is a determinant of liver steatosis and the progression to more severe forms of disease. The present study investigated the effect of paraoxonase-1 (PON1) deficiency on histological alterations and hepatic metabolism in mice fed a high-fat high-cholesterol diet. We performed nontargeted metabolomics on liver tissues from 8 male PON1-deficient mice and 8 wild-type animals fed a high-fat, high-cholesterol diet for 22 weeks.

Monocyte chemoattractant protein-1 and paraoxonase-1 and 3 levels in patients with sepsis treated in an intensive care unit: a preliminary report.

Background: There is considerable interest in the research of molecules modulating the acute inflammatory response in patients with sepsis. Paraoxonases (PON) are antioxidant and anti-inflammatory enzymes that inhibit the production of the monocyte chemoattractant protein-1 (MCP-1). This preliminary study investigated changes in PON status and MCP-1 concentrations in critically ill patients with severe sepsis treated in an ICU and their relationship with the evolution of disease.

Paraoxonase-1 is not associated with coronary artery calcification in type 2 diabetes: results from the PREDICT study.

Objectives: To determine any association between serum paraoxonase-1 (PON1) activity, protein and coding region genetic polymorphisms and coronary artery calcification (CACS) and to determine factors which modulate serum PON1 in type 2 diabetes (T2DM).

Methods And Results: 589 patients (419 Caucasian, 120 South Asian, 50 other) from the PREDICT Study were investigated. All patients were asymptomatic for coronary disease and had established T2DM.

Coincubation of PON1, APO A1, and LCAT increases the time HDL is able to prevent LDL oxidation.

The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown.

Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease.

Objective: There are no data on the relationship between serum paraoxonase-3 (PON3) concentration and atherosclerosis in humans. Our aim was to investigate possible associations, using recently developed methods, in patients with peripheral artery disease (PAD) or coronary artery disease (CAD).

Methods: We studied 118 PAD and 72 CAD patients and 175 healthy volunteers.

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation.

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC).

Effect of dilution on high-density lipoprotein associated paraoxonase-1 activity.

Objectives: To investigate the effects of dilution on high-density lipoprotein (HDL) associated paraoxonase-1 (PON1) activity.

Design And Methods: HDL was prepared by ultracentrifugation, diluted with TRIS buffer pH 8.2 (0-128 fold) and assayed spectrophotometrically for PON1 activity using paraoxon and phenyl acetate.

Serum paraoxonase-3 concentration is associated with the severity of hepatic impairment in patients with chronic liver disease.

Objectives: Research on paraoxonase-3 (PON3) has been hampered by the lack of methods for measurement. This is a pilot study aimed at exploring whether chronic liver impairment is associated with changes in serum PON3 concentrations, and to know whether this measurement may provide useful information to investigate this derangement.

Design And Methods: We studied 110 patients with chronic liver disease (21 minimal changes, 79 chronic hepatitis, 10 cirrhosis) and 356 healthy volunteers.

Cholesteryl-ester transfer protein enhances the ability of high-density lipoprotein to inhibit low-density lipoprotein oxidation.

Therapeutic strategies to increase high-density lipoprotein (HDL) to treat or prevent vascular disease include the use of cholesteryl-ester transfer protein (CETP) inhibitors. Here, we show, to the best of our knowledge for the first time, that addition of CETP to HDL enhances the ability of HDL to inhibit low-density lipoprotein oxidation by ∼ 30% for total HDL and HDL(2) (both P < 0.05) and 75% for HDL(3) (P < 0.

Measurement of serum PON-3 concentration: method evaluation, reference values, and influence of genotypes in a population-based study.

Experimental studies showed that paraoxonase-3 (PON3) retards lipoprotein oxidation. Our objective was to describe a new assay to measure serum PON3 concentrations and report their reference values in a population-based study. The influence of PON3 promoter polymorphisms and their relationships with PON1 and lipid profile were also studied.

Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques.

Background: The paraoxonase (PON) enzyme family comprising PON1, PON2 and PON3 are antioxidant enzymes that degrade bioactive oxidised lipids and are thus antiatherogenic.

Materials And Methods: We investigated the localisation of the PON proteins during the development of atherosclerosis by immunohistochemical analysis.

Results: In normal aortas, PON1 and PON3 were localised to smooth muscle cells (SMC) and endothelial cells.

Tissue distribution and expression of paraoxonases and chemokines in mouse: the ubiquitous and joint localisation suggest a systemic and coordinated role.

A vicious cycle between oxidation and inflammation leads to complications in a growing number of disease states. Knowledge on tissue distribution of chemokines, mediators of inflammatory response, and paraoxonases, with antioxidant and anti-inflammatory actions, may be relevant. Using immunohistochemistry and quantitative real-time PCR we have investigated the distribution of PON1, 2 and 3, CCL2, 7, 8 and 12 and the chemokine receptor CCR2 protein and mRNA in 23 tissues from C57BL/6J mice.

'Dippers' flu' and its relationship to PON1 polymorphisms.

Objectives: Sheep-dippers report an acute flu-like condition (dippers' flu: DF) but the cause and relation to chronic disability are unknown.

Methods: In a case-referent study previously reported, 175 sheep dippers with chronic disability and 234 referents, sheep dippers in good health, completed an interview with information on dipping, type of pesticide used and health for each year 1970-2000 and gave blood for typing of PON1 polymorphisms.

Results: Reports of DF were much higher (66.

Human tissue distribution of paraoxonases 1 and 2 mRNA.

We have studied the distribution of mRNA for paraoxonases (PON) 1 and 2 in 24 human tissues using Gene Expression Panels. PON1 mRNA was restricted to adult kidney, liver, and colon as well as fetal liver, whereas PON2 mRNA was more widely distributed in adult human brain, heart, kidney, spleen, liver, colon, lung, small intestine, muscle, stomach, testis, placenta, salivary, thyroid and adrenal glands, pancreas, skin, and bone marrow, as well as fetal brain and liver. PON2 mRNA was not found in ovary, uterus, or plasma leukocytes using the panels.