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Ectonucleotide Pyrophosphatase/Phosphodiesterase 1

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https://www.readbyqxmd.com/read/27888146/a-rhodium-iii-based-inhibitor-of-autotaxin-with-antiproliferative-activity
#1
Tian-Shu Kang, Wanhe Wang, Hai-Jing Zhong, Jia-Xin Liang, Chung-Nga Ko, Jin-Jian Lu, Xiu-Ping Chen, Dik-Lung Ma, Chung-Hang Leung
BACKGROUND: Cancer of the skin is by far the most common of all cancers. Melanoma accounts for only about 1% of skin cancers but causes a large majority of skin cancer deaths. Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), regulates physiological and pathological functions of lysophosphatidic acid (LPA), and is thus an important therapeutic target. METHODS: We synthesized ten metal-based complexes and a novel cyclometalated rhodium(III) complex 1 was identified as an ATX enzymatic inhibitor using multiple methods, including ATX enzymatic assay, thermal shift assay, western immunoblotting and so on...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27537838/e4orf1-enhances-glucose-uptake-independent-of-proximal-insulin-signaling
#2
Ha-Na Na, Vijay Hegde, Olga Dubuisson, Nikhil V Dhurandhar
Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector...
2016: PloS One
https://www.readbyqxmd.com/read/27467858/effects-of-different-variants-in-the-enpp1-gene-on-the-functional-properties-of-ectonucleotide-pyrophosphatase-phosphodiesterase-family-member-1
#3
Jacqueline Stella, Insa Buers, Koen van de Wetering, Wolfgang Höhne, Frank Rutsch, Yvonne Nitschke
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (E-NPP1), encoded by ENPP1, is a plasma membrane protein that generates inorganic pyrophosphate (PPi ), a physiologic inhibitor of hydroxyapatite formation. In humans, variants in ENPP1 are associated with generalized arterial calcification of infancy, an autosomal-recessive condition causing premature onset of arterial calcification and intimal proliferation resulting in stenoses. ENPP1 variants also cause pseudoxanthoma elasticum characterized by ectopic calcification of soft connective tissues...
November 2016: Human Mutation
https://www.readbyqxmd.com/read/27454315/alkalosis-and-dialytic-clearance-of-phosphate-increases-phosphatase-activity-a-hidden-consequence-of-hemodialysis
#4
Ricardo Villa-Bellosta, Emilio González-Parra, Jesús Egido
BACKGROUND: Extracellular pyrophosphate is a potent endogenous inhibitor of vascular calcification, which is degraded by alkaline phosphatase (ALP) and generated by hydrolysis of ATP via ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1). ALP activity (as routinely measured in clinical practice) represents the maximal activity (in ideal conditions), but not the real activity (in normal or physiological conditions). For the first time, the present study investigated extracellular pyrophosphate metabolism during hemodialysis sessions (including its synthesis via eNPP1 and its degradation via ALP) in physiological conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27406238/enpp1-processes-protein-adp-ribosylation-in-vitro
#5
Luca Palazzo, Casey M Daniels, Joanne E Nettleship, Nahid Rahman, Robert Lyle McPherson, Shao-En Ong, Kazuki Kato, Osamu Nureki, Anthony K L Leung, Ivan Ahel
ADP-ribosylation is a conserved post-translational protein modification that plays a role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of ADP-ribosylation is linked to the physiopathology of several human diseases including cancers, diabetes and neurodegenerative disorders. Protein ADP-ribosylation can be reversed by the macrodomain-containing proteins PARG, TARG1, MacroD1 and MacroD2, which hydrolyse the ester bond known to link proteins to ADP-ribose as well as consecutive ADP-ribose subunits; targeting this bond can thus result in the complete removal of the protein modification or the conversion of poly(ADP-ribose) to mono(ADP-ribose)...
September 2016: FEBS Journal
https://www.readbyqxmd.com/read/27238374/the-enpp1-k121q-polymorphism-is-associated-with-type-2-diabetes-and-related-metabolic-phenotypes-in-a-taiwanese-population
#6
Tun-Jen Hsiao, Eugene Lin
Increased risk of developing type 2 diabetes (T2D) has been associated with a single nucleotide polymorphism (SNP), rs1044498 (K121Q), in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, but this association is unclear among Asians. In this replication study, we reassessed whether the ENPP1 rs1044498 SNP is associated with T2D, obesity, and T2D/obesity-related metabolic traits in a Taiwanese population. A total of 1513 Taiwanese subjects were assessed in this study. The ENPP1 rs1044498 SNP was genotyped by the Taqman assay...
September 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27219689/association-of-k121q-polymorphism-in-ectonucleotide-pyrophosphatase-phosphodiesterase-1-with-clinical-characteristics-of-metabolic-syndrom
#7
N Li, H Pan, M Cui, Q Li
PURPOSE: This study aimed to investigate the relationships between K121Q polymorphism of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and clinical characteristics of metabolic syndrome (MS) in northern Han Chinese. MATERIALS AND METHODS: A total of 209 MS patients and 248 healthy controls of Han ethnic group in northern China were enrolled in this study. Various clinical parameters of these participants were firstly collected and compared, including age, sex, body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressures (SBP/DBP), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance index (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density and low-density lipoprotein cholesterol (LDL-C/HDL-C)...
May 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/27187064/corpus-luteum-as-a-novel-target-of-weight-changes-that-contribute-to-impaired-female-reproductive-physiology-and-function
#8
Satu Kuokkanen, Alex J Polotsky, Justin Chosich, Andrew P Bradford, Anna Jasinska, Tzu Phang, Nanette Santoro, Susan E Appt
UNLABELLED: Obesity and malnutrition are associated with decreased fecundity in women. Impaired reproductive capacity in obese women is often attributed to anovulation. However, obese women with ovulatory cycles also have reduced fertility, but the etiology of their impaired reproduction is only partially understood. Accumulating evidence suggests that obesity directly impairs oocyte and embryo quality as well as endometrial receptivity. In obese women, urinary progesterone metabolite excretion is decreased, but in excess of what can be explained by suppressed gonadotropin secretion, suggesting that apart from its central effect obesity may directly affect progesterone (P4) production...
August 2016: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/27086348/interleukin-1%C3%AE-suppresses-the-transporter-genes-ank-and-ent1-expression-in-stromal-progenitor-cells-retaining-mineralization
#9
Yoichi Ezura, Xin Lin, Arina Hatta, Yayoi Izu, Masaki Noda
Heterotopic ossification (HO) in various tissues evokes clinical problems. Inflammatory responses of the stromal progenitor cells may be involved in its etiology. Previous report indicated that pro-inflammatory cytokines including IL-1β enhanced the in vitro calcification of human mesenchymal stem cells (MSCs), by suppressing the expression of ectonucleotide pyrophosphatase/phosphodiesterase-1 gene (ENPP1). However, possible contribution of other related factors had not been investigated. Here, we investigated the expression of regulators of extracellular pyrophosphate and nucleosides including Enpp1, Nt5e, Ank, Enptds, and Ent1, examining various connective tissue stromal progenitor cells, including bone marrow stromal cells and synovium derived cells from mouse, or bone marrow MSCs from human...
August 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27029896/plasma-cell-alloantigen-enpp1-is-expressed-by-a-subset-of-human-b-cells-with-potential-regulatory-functions
#10
Jeongheon Yoon, Hongsheng Wang, Yong Chan Kim, Momoko Yoshimoto, Sadia Abbasi, Herbert C Morse Iii
Plasma cell alloantigen 1 (PC1), also known as ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1), is an enzyme involved primarily in hydrolysis of adenosine triphosphate at the cell surface. Although the expression pattern of PC1 is relatively broad, its expression in B cells is found at significant levels only in terminally differentiated germinal center B cells, plasma cells and a subset of B-1a cells in mice. Here we describe studies designed to determine whether expression of PC1 might define novel populations of human B cells with similarities to mouse B cells...
September 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/26958016/contribution-of-enpp1-tcf7l2-and-fto-polymorphisms-to-type-2-diabetes-in-mixed-ancestry-ethnic-population-of-south-africa
#11
Yandiswa Y Yako, Jabulisile H Madubedube, Andre P Kengne, Rajiv T Erasmus, Tahir S Pillay, Tandi E Matsha
BACKGROUND: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. OBJECTIVES: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. METHODS: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits...
December 2015: African Health Sciences
https://www.readbyqxmd.com/read/26861177/antidepressant-behavior-in-thyroidectomized-wistar-rats-is-induced-by-hippocampal-hypothyroidism
#12
Rodrigo Rodrigues da Conceição, Roberto Laureano-Melo, Kelen Carneiro Oliveira, Maria Clara de Carvalho Melo, Tereza Sayoko Kasamatsu, Rui Monteiro de Barros Maciel, Janaina Sena de Souza, Gisele Giannocco
Thyroidectomy is a surgical procedure indicated in cases of several maligned or benign thyroid diseases, thus, the aim of our study was to verify how the hypothyroidism induced by thyroidectomy influences behavioral parameters and its relation to thyroid hormones metabolism and neurogenesis at hippocampus. For this purpose, Adult male Wistar rats underwent to thyroidectomy to induce hypothyroidism. Behavioral tests, the thyroid profile and hippocampal gene expression were evaluated in control and in thyroidectomized animals...
April 1, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/26792705/abnormal-mechanical-loading-induces-cartilage-degeneration-by-accelerating-meniscus-hypertrophy-and-mineralization-after-acl-injuries-in-vivo
#13
Guoqing Du, Hongsheng Zhan, Daofang Ding, Shaowei Wang, Xiaochun Wei, Fangyuan Wei, Jianzhong Zhang, Bahar Bilgen, Anthony M Reginato, Braden C Fleming, Jin Deng, Lei Wei
BACKGROUND: Although patients with an anterior cruciate ligament (ACL) injury have a high risk of developing posttraumatic osteoarthritis (PTOA), the role of meniscus hypertrophy and mineralization in PTOA after an ACL injury remains unknown. PURPOSE/HYPOTHESIS: The purpose of this study was to determine if menisci respond to abnormal loading and if an ACL injury results in meniscus hypertrophy and calcification. The hypotheses were that (1) abnormal mechanical loading after an ACL injury induces meniscus hypertrophy and mineralization, which correlates to articular cartilage damage in vivo, and (2) abnormal mechanical loading on bovine meniscus explants induces the overexpression of hypertrophic and mineralization markers in vitro...
March 2016: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/26494600/donor-s-age-and-replicative-senescence-favour-the-in-vitro-mineralization-potential-of-human-fibroblasts
#14
Federica Boraldi, Angelica Bartolomeo, Caterina Di Bari, Andrea Cocconi, Daniela Quaglino
Aberrant mineralization of soft connective tissues (ectopic calcification) may occur as a frequent age-related complication. Still, it remains unclear the role of mesenchymal cell donor's age and of replicative senescence on ectopic calcification. Therefore, the ability of cells to deposit in-vitro hydroxyapatite crystals and the expression of progressive ankylosis protein homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), tissue non specific alkaline phosphatase (TNAP) and osteopontin (OPN) have been evaluated in human dermal fibroblasts derived from neonatal (nHDF) and adult (aHDF) donors (ex-vivo ageing model) or at low and high cumulative population doublings (CPD) up to replicative senescence (in-vitro ageing model)...
December 2015: Experimental Gerontology
https://www.readbyqxmd.com/read/26406452/inhibition-of-osteoblast-mineralization-by-phosphorylated-phage-derived-apatite-specific-peptide
#15
Janani Ramaswamy, Hwa Kyung Nam, Harsha Ramaraju, Nan E Hatch, David H Kohn
Functionalization of biomaterials with material- and cell-specific peptide sequences allows for better control of their surface properties and communication with the surrounding environment. Using a combinatorial phage display approach, we previously identified the peptide VTKHLNQISQSY (VTK) with specific affinity to biomimetic apatite. Phosphorylation of the serine residues of the peptide (pVTK) caused a significant increase in binding to apatite, as well as a dose-dependent inhibition of osteoblast mineralization...
December 2015: Biomaterials
https://www.readbyqxmd.com/read/26219706/genetically-modified-mice-for-studying-tnap-function
#16
REVIEW
Sonoko Narisawa
Genetically modified mice are powerful tools for understanding the functions of genes and proteins and often serve as models of human disease. Here, several knockout and transgenic mouse lines related to tissue-nonspecific alkaline phosphatase (TNAP) are described. Conventional TNAP knockout mice die before weaning and show vitamin B6 dependent epilepsy and impaired bone mineralization, mimicking infantile hypophosphatasia. Administration of recombinant human TNAP rescues the lethal phenotype and improves bone mineralization in the null knockout mice, and this enzyme replacement therapy has been successfully applied to the treatment of human patients...
2015: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/26113370/enzyme-assays-for-synthesis-and-degradation-of-2-5as-and-other-2-5-oligonucleotides
#17
Jesper Buchhave Poulsen, Karina Hansen Kjær, Just Justesen, Pia Møller Martensen
BACKGROUND: The 5'-triphosphorylated, 2'-5'-linked oligoadenylate polyribonucleotides (2-5As) are central to the interferon-induced antiviral 2-5A system. The 2-5As bind and activate the RNase L, an endoRNase degrading viral and cellular RNA leading to inhibition of viral replication. The 2-5A system is tightly controlled by synthesis and degradation of 2-5As. Whereas synthesis is mediated by the 2'-5' oligoadenylate synthetase family of enzymes, degradation seems to be orchestrated by multiple enzyme nucleases including phosphodiesterase 12, the ectonucleotide pyrophosphatase/phosphodiesterase 1 and the A-kinase anchoring protein 7...
June 26, 2015: BMC Biochemistry
https://www.readbyqxmd.com/read/26065921/loss-of-microrna-27b-contributes-to-breast-cancer-stem-cell-generation-by-activating-enpp1
#18
Ryou-u Takahashi, Hiroaki Miyazaki, Fumitaka Takeshita, Yusuke Yamamoto, Kaho Minoura, Makiko Ono, Makoto Kodaira, Kenji Tamura, Masaki Mori, Takahiro Ochiya
Cancer stem cells (CSCs) have been identified in various types of cancer; however, the mechanisms by which cells acquire CSC properties such as drug resistance and tumour seeding ability are not fully understood. Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development...
2015: Nature Communications
https://www.readbyqxmd.com/read/26054852/the-venomous-cocktail-of-the-vampire-snail-colubraria-reticulata-mollusca-gastropoda
#19
Maria Vittoria Modica, Fabrizio Lombardo, Paolo Franchini, Marco Oliverio
BACKGROUND: Hematophagy arose independently multiple times during metazoan evolution, with several lineages of vampire animals particularly diversified in invertebrates. However, the biochemistry of hematophagy has been studied in a few species of direct medical interest and is still underdeveloped in most invertebrates, as in general is the study of venom toxins. In cone snails, leeches, arthropods and snakes, the strong target specificity of venom toxins uniquely aligns them to industrial and academic pursuits (pharmacological applications, pest control etc...
2015: BMC Genomics
https://www.readbyqxmd.com/read/25988856/new-insights-into-heterogeneity-of-peritoneal-b-1a-cells
#20
REVIEW
Hongsheng Wang, Jian-xin Lin, Peng Li, Jeff Skinner, Warren J Leonard, Herbert C Morse
Peritoneal B-1a cells are characterized by their expression of CD5 and enrichment for germline-encoded IgM B cell receptors. Early studies showing expression of a diverse array of VDJ sequences among purified B-1a cells provided a molecular basis for understanding the heterogeneity of the B-1a cell repertoire. Antigen-driven positive selection and the identification of B-1a specific progenitors suggest multiple origins of B-1a cells. The introduction of new markers such as PD-L2, CD25, CD73, and PC1 (plasma cell alloantigen 1, also known as ectonucleotide phosphodiesterase/pyrophosphatase 1) further helped to identify phenotypically and functionally distinct B-1a subsets...
December 2015: Annals of the New York Academy of Sciences
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