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Mohammad Hassan Golzari, Mohammad Hassan Javanbakht, Ehsan Ghaedi, Hamed Mohammadi, Mahmoud Djalali
Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM...
January 2019: Clinical Nutrition Research
Diana M Shih, Yonghong Meng, Tamer Sallam, Laurent Vergnes, Michelle L Shu, Karen Reue, Peter Tontonoz, Alan M Fogelman, Aldons J Lusis, Srinivasa T Reddy
(1) Background: Paraoxonase 2 (PON2) is a ubiquitously expressed protein localized to endoplasmic reticulum and mitochondria. Previous studies have shown that PON2 exhibits anti-oxidant and anti-inflammatory functions, and PON2-deficient (PON2-def) mice are more susceptible to atherosclerosis. Furthermore, PON2 deficiency leads to impaired mitochondrial function. (2) Methods: In this study, we examined the susceptibility of PON2-def mice to diet-induced obesity. (3) Results: After feeding of an obesifying diet, the PON2-def mice exhibited significantly increased body weight due to increased fat mass weight as compared to the wild-type (WT) mice...
January 11, 2019: Antioxidants (Basel, Switzerland)
Q Liu, H Liu, H Bai, W Huang, R Zhang, J Tan, L Guan, P Fan
PURPOSE: To investigate the relationship between superoxide dismutase 2 (SOD2) A16V and paraoxonase 2 (PON2) S311C gene variants and the risk of polycystic ovary syndrome (PCOS) and evaluate the effects of the genotypes on clinical, hormonal, metabolic and oxidative stress indexes in Chinese women. METHODS: This is a cross-sectional study of 932 patients with PCOS and 745 control women. For the clinical and metabolic association study of genotypes, 631 patients and 492 controls were included after excluding the subjects with interferential factors...
January 3, 2019: Journal of Endocrinological Investigation
Shrijana Shrestha, Vijay Kumar Singh, Sajib Kumar Sarkar, Balasubramanian Shanmugasundaram, Kadirvelu Jeevaratnam, Bidhan Chandra Koner
Biochemical basis of Malathion exposure-induced diabetes mellitus is not known. Hence, effects of its sub-toxic exposure on redox sensitive kinases (RSKs), insulin signaling and insulin-induced glucose uptake were assessed in rat muscle cell line. In this in vitro study, rat myoblast (L6) cells were differentiated to myotubes and were exposed to sub-toxic concentrations (10 mg/l and 20 mg/l) of Malathion for 18 hours. Total antioxidant level and insulin-stimulated glucose uptake by myotubes were assayed...
November 29, 2018: Drug and Chemical Toxicology
M I Shakhparonov, N V Antipova, V O Shender, P V Shnaider, G P Arapidi, N B Pestov, M S Pavlyukov
PON2 belongs to the paraoxonase protein family that consists of lactone hydrolyzing enzymes with different substrate specificities. Unlike other members of the family, PON2 exhibits substantial antioxidant activity, is localized predominantly inside the cell, and is ubiquitously expressed in all human tissues. Previously, it was proffered that defense against pathogens, such as Pseudomonas aeruginosa , is the main function of paraoxonases. However, recent findings have highlighted the important role played by PON2 in protection against oxidative stress, inhibition of apoptosis, and progression of various types of malignancies...
July 2018: Acta Naturae
John F Teiber, Junhui Xiao, Gerald L Kramer, Seiji Ogawa, Christian Ebner, Helene Wolleb, Erick M Carreira, Diana M Shih, Robert W Haley
The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities. However, their physiological function(s) and native substrates are uncertain. Previous structure-activity relationship studies demonstrate that PONs have a high specificity for lipophilic lactones, suggesting that such compounds may be representative of native substrates. This report describes the ability of PONs to hydrolyze two bioactive δ-lactones derived from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and cyclo-epoxycyclopentenone (cyclo-EC)...
September 18, 2018: Biochemical and Biophysical Research Communications
Renato Assis Machado, Carolina de Oliveira Silva, Darlene Camati Persuhn, Vanessa de Melo Cavalcanti Dantas, Silvia Regina de Almeida Reis, Tao Wu, Sergio Roberto Line, Hercilio Martelli-Junior, Edgard Graner, Ricardo D Coletta
During development, oxidative stress is hypothesized to mediate embryotoxicity, which may be intensified by exposition to environmental factors and by genetic variations in the enzymes involved in protecting cells from these damaging effects, including superoxide dismutase (SOD) and paraoxonase (PON). The aim of this study was to evaluate the influence of single-nucleotide polymorphisms (SNP) in genes associated with the neutralization of oxidative stress (SOD and PON family members) in the risk of nonsyndromic oral cleft in the Brazilian population...
September 21, 2018: Environmental and Molecular Mutagenesis
Huan Ren, Sheng-Lan Tan, Mou-Ze Liu, Hoan L Banh, Jian-Quan Luo
Background: The association between paraoxonase 2 (PON2) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been extensively investigated in the Chinese population with conflicting results. In this study, we systematically evaluated the association between PON2 Ser311Cys and Ala148Gly polymorphisms and T2DM risk by pooling all relevant studies. Methods: We searched PubMed, Embase, CNKI, and Wanfang databases for the studies. The strength of association was determined by the allelic, homozygous, heterozygous, recessive, and dominant genetic models and measured as odds ratio (OR) and 95% confidence interval (CI), under fixed- or random-effect models...
2018: Frontiers in Endocrinology
Ingvild Oma, Ole Kristoffer Olstad, Jacqueline Kirsti Andersen, Torstein Lyberg, Øyvind Molberg, Ida Fostad, Morten Wang Fagerland, Sven Martin Almdahl, Stein Erik Rynning, Arne Yndestad, Pål Aukrust, Jon Elling Whist, Ivana Hollan
BACKGROUND: Vitamin D has an important role in the immune system, and has been linked to rheumatoid arthritis (RA) and coronary artery disease (CAD). The exact mechanisms by which vitamin D is involved in these processes are still unclear. Therefore, we wanted to search for differences in expression of genes involved in the vitamin D receptor (VDR) activation pathway and genes that are known to alter upon vitamin D stimulation, in the aortic adventitia of CAD patients with and without RA...
2018: PloS One
Eman R Abd Elgwad, Eman G Behiry, Fathy M Swailem, Seham G Ameen, Dalia M Abdelhasib, Rabab O Abd Elhamid
Introduction: Paraoxonases are a group of different forms enzymes that consist of three non-similar isoforms, PON1, PON2 and PON3 , which are located near to each other on the long arm of chromosome7. This study aims to investigate the association of a Q192R polymorphism of PON1 gene and statin response in patients with ischemic heart disease with dyslipidemia. Methods: The studied population included three hundred patients with coronary artery disease with dyslipidemia who were prescribed statins...
July 2018: Annals of Medicine and Surgery
Levent Dikbas, Riza Dur, İsmail Hakkı Tas, Ömer Erkan Yapça, Neslihan Dikbas
OBJECTIVE: Oxidative stress has been reported to be associated with various pregnancy complications and to play key roles in many of them. An inadequate level of antioxidant defense may eventually lead to an early pregnancy loss. There is a lack of information about the roles of the PON2 and PON3 enzymes in the etiology of the cases of unexplained recurrent abortus. The aim of our study is to determine and present the data regarding the roles of these enzymes for the first time. MATERIALS AND METHODS: We measured the transcriptional levels of the PON2 and PON3 enzymes in the curettage materials obtained from the patients with unexplained recurrent abortus (n=25) and compared the results with those measured in the abortus materials from healthy pregnant women (n=50) who had undergone a voluntary abortion...
June 15, 2018: Journal of Gynecology Obstetrics and Human Reproduction
Nan Wu, Guili Liu, Yi Huang, Qi Liao, Liyuan Han, Huandan Ye, Shiwei Duan, Xiaomin Chen
OBJECTIVE: Blood lipids are well-known risk factors for coronary heart disease (CHD). The aim of this study was to explore the association between 17 lipid-related gene polymorphisms and CHD. METHODS: The current study examined with 784 CHD cases and 739 non-CHD controls. Genotyping was performed on the MassARRAY iPLEX® assay platform. RESULTS: Our analyses revealed a significant association of APOE rs7259620 with CHD (genotype: χ2=6.353, df=2, p=0...
June 2018: Anatolian Journal of Cardiology
Abdolkarim Mahrooz, Mohammad Bagher Hashemi-Soteh, Masoud Heydari, Ruzbeh Boorank, Fatemeh Ramazani, Ali Mahmoudi, Anvarsadat Kianmehr, Ahad Alizadeh
OBJECTIVE: Genome studies have shown that the genes encoding paraoxonase 1 (PON1) and PON2 are associated with glucose metabolism. The goal of this study was to simultaneously evaluate the association between functional variants in PON1 and PON2 genes and susceptibility for type 2 diabetes (T2D) and determine whether they can affect glycemic control. METHODS: We performed a case-control study with 145 newly diagnosed patients with T2D and 148 controls. The common variants including PON1-Q192R, PON1-L55M and PON2-S311C were genotyped by PCR-based RFLP...
September 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Wei Li, David Kennedy, Zhili Shao, Xi Wang, Andre Klaassen Kamdar, Malory Weber, Kayla Mislick, Kathryn Kiefer, Rommel Morales, Brendan Agatisa-Boyle, Diana M Shih, Srinivasa T Reddy, Christine S Moravec, W H Wilson Tang
BACKGROUND: Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. METHODS AND RESULTS: Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression...
June 2018: Free Radical Biology & Medicine
Shiyu Tao, Liqiong Niu, Liuping Cai, Yali Geng, Canfeng Hua, Yingdong Ni, Ruqian Zhao
AIMS: The quorum-sensing molecule N‑(3‑oxododecanoyl)‑l‑homoserine lactone (C12-HSL), produced by the Gram negative human pathogenic bacterium Pseudomonas aeruginosa, modulates mammalian cell behavior. Our previous findings suggested that C12-HSL rapidly decreases viability and induces apoptosis in LS174T goblet cells. MAIN METHODS: In this study, the effects of 100 μM C12-HSL on mitochondrial function and cell proliferation in LS174T cells treated for 4 h were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry...
May 15, 2018: Life Sciences
Asokan Devarajan, Feng Su, Victor Grijalva, Meghna Yalamanchi, Ashna Yalamanchi, Feng Gao, Hannah Trost, Josephine Nwokedi, Gina Farias-Eisner, Robin Farias-Eisner, Alan M Fogelman, Srinivasa T Reddy
Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue...
March 12, 2018: Cell Death & Disease
Thelma Beatriz González-Castro, Carlos Alfonso Tovilla-Zárate, Isela Esther Juárez-Rojop, Yazmín Hernández-Díaz, María Lilia López-Narváez, Candelario Rodríguez-Pérez, Yahaira Karina González-Hernández, Miguel Ángel Ramos-Méndez
AIM: Investigate the correlation between paraoxonase 2 (PON2) Ser311Cys polymorphism as well as the peroxisome proliferator-activated receptor gamma (PPARG) His477His polymorphism and the susceptibility to development of coronary heart diseases (CHD) through a meta-analysis. METHODS: Odds ratio and the corresponding 95% CI were used to assess the results. We included 7476 CHD patients and 8504 healthy controls. All the statistical analyses were performed by Comprehensive Meta-Analysis software (CMA, version 2...
March 2018: Biomarkers in Medicine
Carlos Moya, Salvador Máñez
Atherosclerosis is one of the leading causes of death in Western countries, with high-density lipoproteins (HDL) playing an important protective role due to their ability to inhibit oxidation of low-density lipoproteins (LDL), thus relieving vascular subendothelial damage. One of the proteins constituting HDL particles is paraoxonase-1 (PON1), an enzyme able to hydrolyze aryl esters, lactones, and organophosphates. Other closely related paraoxonases are designated as PON2, which is a protein localized inside many different kinds of cells, and PON3, not only present in HDL but also in mitochondria and endoplasmic reticulum, as well...
April 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Fiona Peris-Sampedro, Jordi Blanco, Maria Cabré, Pia Basaure, Laia Guardia-Escote, Jose L Domingo, Domènec J Sánchez, Maria Teresa Colomina
Recently, we have provided evidence, suggesting that mice expressing the human apolipoprotein E3 (apoE3) are more prone to develop an obesity-like phenotype and a diabetic profile when subchronically fed a chlorpyrifos (CPF)-supplemented diet. The aim of the current study was to examine the underlying mechanisms through which CPF alters both insulin- and leptin-signalling pathways in an APOE-dependent manner. Both adult apoE3- and E4-targeted replacement and C57BL/6 mice were exposed to CPF at 0 or 2 mg/kg body weight/day through the diet for 8 consecutive weeks...
May 2018: Archives of Toxicology
Mahmood Faraz, Carl Herdenberg, Camilla Holmlund, Roger Henriksson, Håkan Hedman
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors...
March 2, 2018: Journal of Biological Chemistry
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