scholarly journals A long and winding road: defining the biological role and clinical importance of paraoxonases

2006 ◽  
Vol 44 (9) ◽  
Author(s):  
Richard W. James
Keyword(s):  
Clinical Importance ◽  
Protective Role ◽  
Biological Role ◽  
Paraoxonase 1 ◽  
Mammalian Evolution ◽  
Lipoprotein Lipid ◽  
Primary Activity ◽  
Member Gene ◽  
Clinical Interest ◽  
Biological Substrates

AbstractParaoxonase-1 (PON1) is an enzyme belonging to a three-member gene family, each of which is highly conserved in mammalian evolution. Whilst there is consensus that the paraoxonase family members have a general protective influence, their precise biological role has remained elusive. A toxicological role, protecting from environmental poisoning by organophosphate derivatives, drove much of the earlier work on the enzymes. More recently, clinical interest has focused on a protective role in vascular disease via a hypothesised impact on lipoprotein lipid oxidation. Recent confirmation that the primary activity of the paraoxonases is that of a lactonase considerably expands the potential sources of biological substrates for the enzyme. Studies on such substrates may shed further light on different mechanisms by which paraoxonases beneficially influence atherosclerosis, as well as defining possible roles in limiting bacterial infection and in innate immunity.Clin Chem Lab Med 2006;44:1052–9.

scholarly journals Paraoxonase-1 Inhibits Oxidized Low-Density Lipoprotein-Induced Metabolic Alterations and Apoptosis in Endothelial Cells: A Nondirected Metabolomic Study

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anabel García-Heredia ◽  
Judit Marsillach ◽  
Anna Rull ◽  
Iris Triguero ◽  
Isabel Fort ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Current Knowledge ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Wild Type Mouse ◽  
Protective Role ◽  
Paraoxonase 1 ◽  
Wild Type ◽  
Metabolic Alterations ◽  
Deficient Mice

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. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.

scholarly journals Paraoxonase-1 as a Regulator of Glucose and Lipid Homeostasis: Impact on the Onset and Progression of Metabolic Disorders

2019 ◽  
Vol 20 (16) ◽  
pp. 4049 ◽  
Author(s):  
Meneses ◽  
Silvestre ◽  
Sousa-Lima ◽  
Macedo
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disorders ◽  
Physiological Role ◽  
Normal Activity ◽  
Protective Role ◽  
Paraoxonase 1 ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Homeostasis ◽  
The Impact ◽  
And Oxidative Stress

Metabolic disorders are characterized by an overall state of inflammation and oxidative stress, which highlight the importance of a functional antioxidant system and normal activity of some endogenous enzymes, namely paraoxonase-1 (PON1). PON1 is an antioxidant and anti-inflammatory glycoprotein from the paraoxonases family. It is mainly expressed in the liver and secreted to the bloodstream, where it binds to HDL. Although it was first discovered due to its ability to hydrolyze paraoxon, it is now known to have an antiatherogenic role. Recent studies have shown that PON1 plays a protective role in other diseases that are associated with inflammation and oxidative stress, such as Type 1 and Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease. The aim of this review is to elucidate the physiological role of PON1, as well as the impact of altered PON1 levels in metabolic disorders.

scholarly journals Serum Cystatin C Is a Determinant of Paraoxonase Activity in Hemodialyzed and Renal Transplanted Patients

2009 ◽  
Vol 26 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Éva Varga ◽  
Ildikó Seres ◽  
Mariann Harangi ◽  
Ferenc Sztanek ◽  
László Asztalos ◽  
...  
Keyword(s):  
Renal Failure ◽  
Cystatin C ◽  
Sandwich Elisa ◽  
Thiobarbituric Acid ◽  
Protective Role ◽  
Paraoxonase 1 ◽  
Ldl Oxidation ◽  
Pon1 Activity ◽  
Serum Cystatin C ◽  
The Relationship

Background: Human paraoxonase-1 (PON1) inhibits LDL-oxidation and atherogenesis, and possesses lactonase activity. Decreased PON1 activity was found in hemodialyzed and renal transplanted patients. Cystatin C plays a protective role in atherosclerosis, and is a new, sensitive marker of renal function. The relationship between these two markers in renal failure has not been investigated.Aims: The goal of this study was to clarify the relationship between PON1 activity, cystatin C and homocysteine in chronic renal failure. We also determined the levels of oxidatively modified LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) to characterize lipid peroxidation.Patients and methods: 74 hemodialized (HD), 171 renal transplanted patients (TRX), and 110 healthy controls (C) were involved in the study. PON1 activity and TBARS levels were measured spectrophotometrically. OxLDL level was determined with sandwich ELISA.Results: There was a negative correlation between PON1 activity and cystatin C level. Homocysteine level correlated negatively with PON1 activity, and positively with cystatin C level. OxLDL and TBARS levels were significantly higher in the HD and TRX groups compared to C.Conclusions: Cystatin C may be a good predictive factor not only for homocysteine levels but for the antioxidant status in patients with renal failure and renal transplantation.

scholarly journals The contribution of paraoxonase 1 and myeloperoxidase to HDL-cholesterol functionality

2016 ◽  
Vol 8 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Marzena Malara ◽  
Anna Kęska ◽  
Grażyna Lutosławska
Keyword(s):  
Ldl Cholesterol ◽  
Scientific Evidence ◽  
Protective Action ◽  
Hdl Cholesterol ◽  
Protective Role ◽  
Plasma Lipoproteins ◽  
Paraoxonase 1 ◽  
Increased Risk

SummaryThe purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol) bring about atherosclerosis and an increased risk of cardiovascular disease (CVD) which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C) and increasing the HDL-cholesterol (HDL-C). However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1) and myeloperoxidase (MPO) – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

scholarly journals Distribution of Paraoxonase-1 (PON-1) and Lipoprotein Phospholipase A2 (Lp-PLA2) across Lipoprotein Subclasses in Subjects with Type 2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Angelina Passaro ◽  
Giovanni Battista Vigna ◽  
Arianna Romani ◽  
Juana M. Sanz ◽  
Carlotta Cavicchio ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Protective Role ◽  
Lipoprotein Cholesterol ◽  
Paraoxonase 1 ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein Subclasses

Paraoxonase-1 (PON1) and lipoprotein phospholipase A2 (Lp-PLA2) may exert an important protective role by preventing the oxidative transformation of high- and low-density lipoproteins (HDL and LDL, respectively). The activity of both enzymes is influenced by lipidome and proteome of the lipoprotein carriers. T2DM typically presents significant changes in the molecular composition of the lipoprotein subclasses. Thus, it becomes relevant to understand the interaction of PON1 and Lp-PLA2 with the subspecies of HDL, LDL, and other lipoproteins in T2DM. Serum levels of PON1-arylesterase and PON1-lactonase and Lp-PLA2 activities and lipoprotein subclasses were measured in 202 nondiabetic subjects (controls) and 92 T2DM outpatients. Arylesterase, but not lactonase or Lp-PLA2 activities, was inversely associated with TD2M after adjusting for potential confounding factors such as age, sex, smoking, body mass index, hypertension, and lipoprotein subclasses (odds ratio = 3.389, 95% confidence interval 1.069–14.756). Marked difference between controls and T2DM subjects emerged from the analyses of the associations of the three enzyme activities and lipoprotein subclasses. Arylesterase was independently related with large HDL-C and small intermediate-density lipoprotein cholesterol (IDL-C) in controls while, along with lactonase, it was related with small low-density lipoprotein cholesterol LDL-C, all IDL-C subspecies, and very low-density lipoprotein cholesterol (VLDL-C) in T2DM (p<0.05for all). Concerning Lp-PLA2, there were significant relationships with small LDL-C, large IDL-C, and VLDL-C only among T2DM subjects. Our study showed that T2DM subjects have lower levels of PON1-arylesterase compared to controls and that T2DM occurrence may coincide with a shift of PON1 and Lp-PLA2 towards the more proatherogenic lipoprotein subclasses. The possibility of a link between the two observed phenomena requires further investigations.

scholarly journals Factors of the Lectin Pathway of Complement Activation and Their Clinical Associations in Neonates

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maciej Cedzynski ◽  
Anna St. Swierzko ◽  
David C. Kilpatrick
Keyword(s):  
Gestational Age ◽  
Serine Proteases ◽  
Low Birthweight ◽  
Clinical Importance ◽  
Protective Role ◽  
High Serum ◽  
Lectin Pathway ◽  
Protein Levels ◽  
Mannan Binding Lectin ◽  
Low Serum

This paper summarizes the data concerning soluble defense lectins (mannan-binding lectin, M-ficolin, L-ficolin, and H-ficolin) with the unique ability to activate complement and their associated serine proteases (MASPs) in neonates. The clinical importance of deficiencies of these immune factors is presented in aspects of perinatal mortality, premature births, and low birthweight. Prenatal serum concentrations of L-ficolin, H-ficolin, and MASP-2 (and probably M-ficolin) correlate with gestational age and birthweight. The relationship of serum MBL to gestational age is controversial. TheMBL2genotypes XA/O and O/O (associated with low-serum MBL) are associated with perinatal infections, whereas the high serum MBL-conferring A/A genotypes may be associated with prematurity. Low-serum L-ficolin concentrations, but not low-serum H-ficolin concentrations, are also associated with perinatal infections. Much of the literature is inconsistent, and the relationships reported so far require independent confirmation at both gene and protein levels. Our preliminary conclusion is that these soluble defense lectins play a protective role in the neonate, and that insufficiency of such factors contributes to the adverse consequences of prematurity and low birthweight.

scholarly journals Purinergic plasticity within petrosal neurons in hypertension

2018 ◽  
Vol 315 (5) ◽  
pp. R963-R971 ◽  
Author(s):  
Davi J. A. Moraes ◽  
Melina P. da Silva ◽  
Pedro F. Spiller ◽  
Benedito H. Machado ◽  
Julian F. R. Paton
Keyword(s):  
Carotid Body ◽  
Atp Release ◽  
Clinical Importance ◽  
Receptor Expression ◽  
P2x3 Receptors ◽  
Neurogenic Hypertension ◽  
Factors Affecting ◽  
Electrophysiological Properties ◽  
Carotid Bodies ◽  
Clinical Interest

The carotid bodies are peripheral chemoreceptors and contribute to the homeostatic maintenance of arterial levels of O2, CO2, and [H+]. They have attracted much clinical interest recently because of the realization that aberrant signaling in these organs is associated with several pathologies including hypertension. Herein, we describe data suggesting that sympathetic overactivity in neurogenic hypertension is, at least in part, dependent on carotid body tonicity and hyperreflexia that is related to changes in the electrophysiological properties of chemoreceptive petrosal neurons. We present results showing critical roles for both ATP levels in the carotid bodies and expression of P2X3 receptors in petrosal chemoreceptive, but not baroreceptive, terminals in the etiology of carotid body tonicity and hyperreflexia. We discuss mechanisms that may underlie the changes in electrophysiological properties and P2X3 receptor expression in chemoreceptive petrosal neurons, as well as factors affecting ATP release by cells within the carotid bodies. Our findings support the notion of targeting the carotid bodies to reduce sympathetic outflow and arterial pressure, emphasizing the potential clinical importance of modulating purinergic transmission to treat pathologies associated with carotid body dysfunction but, importantly, sparing physiological chemoreflex function.

RENAL RESPONSE OF PREMATURE INFANTS TO ADMINISTRATION OF BICARBONATE AND POTASSIUM

PEDIATRICS ◽  
1954 ◽  
Vol 13 (1) ◽  
pp. 4-14
Author(s):  
FOLKE TUDVAD ◽  
HELEN MCNAMARA ◽  
HENRY L. BARNETT
Keyword(s):  
Premature Infant ◽  
Maximum Rate ◽  
Clinical Importance ◽  
Tubular Reabsorption ◽  
Hydrogen Ion ◽  
Serum Bicarbonate ◽  
Bicarbonate Concentration ◽  
The Third ◽  
Renal Functions ◽  
Clinical Interest

THE OBSERVATIONS to be described were undertaken in an attempt to answer the following questions: 1. Does renal immaturity play a role in the "physiologic" acidosis of the premature infant? 2. Can this acidosis be corrected by the administration of bicarbonate? 3. Is the premature infant able to excrete potassium as readily as the adult? The answers to these questions possess both physiologic and clinical interest. The acidosis of the premature infant has been attributed to increased production of organic acids. However, immaturity of renal functions involving hydrogen ion excretion could be responsible for failure of the infant to correct the acidosis completely. In addition, a decreased maximum rate of tubular reabsorption of bicarbonate due to decreased hydrogen ion excretion would in itself result in a continuous drain on bicarbonate stores. In regard to the second question, it is generally agreed that correction of the "physiologic" acidosis of the premature infant is not indicated. However, further knowledge may reveal circumstances where it is desirable to increase serum bicarbonate. If so, it would be of clinical importance to known whether the serum bicarbonate concentration of the premature infant can be raised to normal adult values by the administration of bicarbonate. If the maximum rate of tubular reabsorption of bicarbonate is decreased, bicarbonate administration would result not in increased serum bicarbonate concentrations but only in increased rate of excretion. The third question has very clear clinical application. Safe treatment of potassium deficiency by the administration of potassium is dependent in large part upon the ability of the kidney to excrete potassium rapidly.

scholarly journals Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ravi Varatharajalu ◽  
Mamatha Garige ◽  
Leslie C. Leckey ◽  
Karina Reyes-Gordillo ◽  
Ruchi Shah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Protective Role ◽  
Chronic Ethanol ◽  
Paraoxonase 1 ◽  
Protective Effects ◽  
Chronic Alcohol ◽  
Ethanol Group ◽  
Homocysteine Thiolactonase

Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories fromω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories fromω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against highω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to highω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with highω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and highω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

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