DOCSLIB.ORG

Supplementary Data 1. Gene Marker Sets in Each Liver Toxicity Phenotype TAA&MP

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Data 1. Gene Marker Sets in Each Liver Toxicity Phenotype TAA&MP Supplementary Data 1. Gene marker sets in each liver toxicity phenotype TAA&MP: 45 probe sets Probe Set ID Gene Symbol Gene Title UniGene ID 1367648_at Igfbp2 insulin-like growth factor binding protein 2 Rn.6813 1367957_at Rgs3 regulator of G-protein signaling 3 Rn.53900 1368520_at Apoa4 apolipoprotein A-IV Rn.15739 1368530_at Mmp12 matrix metallopeptidase 12 Rn.33193 1368778_at Slc6a6 solute carrier family 6 (neurotransmitter transporter, taurine), member 6 Rn.9968 1369783_a_at Nrg1 neuregulin 1 Rn.37438 1369948_at Ngfrap1 nerve growth factor receptor (TNFRSF16) associated protein 1 Rn.3126 1371237_a_at Mt1a metallothionein 1a Rn.54397 1371735_at --- --- --- 1372557_at Arl6 ADP-ribosylation factor-like 6 Rn.101944 1372773_at Npdc1 neural proliferation, differentiation and control, 1 Rn.5802 1373499_at Gas5 growth arrest specific 5 Rn.14733 1373658_at Racgap1 Rac GTPase-activating protein 1 Rn.101301 1373814_at R3hdm2 R3H domain containing 2 Rn.203556 1374071_at Fam118a family with sequence similarity 118, member A Rn.36745 1374265_at --- --- Rn.166593 1374493_at --- --- Rn.19441 1376100_at Tubb6 tubulin, beta 6 Rn.98430 1377686_at --- --- Rn.164584 1378413_at --- --- Rn.146196 1379419_at Tmem184c transmembrane protein 184C Rn.12069 1380533_at App amyloid beta (A4) precursor protein Rn.2104 1382186_a_at Gpatch4 G patch domain containing 4 Rn.20166 1382604_at Polr3g polymerase (RNA) III (DNA directed) polypeptide G Rn.147190 1383434_at Pycr1 pyrroline-5-carboxylate reductase 1 Rn.99704 1383906_at Neurl3 neuralized homolog 3 (Drosophila) Rn.17894 1384449_at --- --- Rn.11851 1386879_at Lgals3 lectin, galactoside-binding, soluble, 3 Rn.764 1387925_at Asns asparagine synthetase Rn.11172 1388210_at Acot2 acyl-CoA thioesterase 2 Rn.37524 1388666_at Enc1 ectodermal-neural cortex 1 Rn.3039 1388900_at --- --- --- 1389221_at Mmd2 monocyte to macrophage differentiation-associated 2 Rn.154557 1389230_at --- --- Rn.4302 1389409_at Tes testis derived transcript Rn.44847 1390232_at RGD1311946 similar to RIKEN cDNA 1810055G02 Rn.16921 1391187_at Ppl periplakin Rn.25259 1392899_at Prc1 protein regulator of cytokinesis 1 Rn.138438 1393252_at --- --- Rn.165372 1393826_at Apon apolipoprotein N Rn.18716 1394948_at --- --- Rn.4302 1395557_at --- --- Rn.166059 1397300_at --- --- Rn.42112 1397409_s_at Wee1 wee 1 homolog (S. pombe) Rn.208255 1398602_at Mad2l1 MAD2 mitotic arrest deficient-like 1 (yeast) Rn.19771 Supplementary Data 1. (continued) Gene marker sets in each liver toxicity phenotaype WY&CFB: 52 probe sets Probe Set ID Gene Symbol Gene Title UniGene ID 1367660_at Fabp3 fatty acid binding protein 3, muscle and heart Rn.32566 1367668_a_at Scd stearoyl-CoA desaturase (delta-9-desaturase) Rn.83595 1367742_at Cpt1b carnitine palmitoyltransferase 1b, muscle Rn.6028 1368037_at Cbr1 carbonyl reductase 1 Rn.3425 1368102_at Hsd11b2 hydroxysteroid 11-beta dehydrogenase 2 Rn.10186 1368143_at Anxa7 annexin A7 Rn.106184 1368171_at Lox lysyl oxidase Rn.11372 1368172_a_at Lox lysyl oxidase Rn.11372 1368177_at Acsl3 acyl-CoA synthetase long-chain family member 3 Rn.54820 1368306_at Grin2c glutamate receptor, ionotropic, N-methyl D-aspartate 2C Rn.9709 1368317_at Aqp7 aquaporin 7 Rn.11111 1368453_at Fads2 fatty acid desaturase 2 Rn.162483 1368509_at Bbs2 Bardet-Biedl syndrome 2 Rn.15987 1368544_a_at Nol3 nucleolar protein 3 (apoptosis repressor with CARD domain) Rn.86956 1368888_a_at Rtn4 reticulon 4 Rn.1348 1369973_at Xdh xanthine dehydrogenase Rn.202951 1370043_at Alcam activated leukocyte cell adhesion molecule Rn.5789 1370164_at Hadha hydroxyacyl-Coenzyme A dehydrogenase Rn.3340 1370397_at Cyp4a3 cytochrome P450, family 4, subfamily a, polypeptide 3 Rn.33492 1370605_s_at Lepr leptin receptor Rn.9891 1370803_at Zwint ZW10 interactor Rn.163272 1370813_at Gstm5 glutathione S-transferase, mu 5 Rn.9158 1370818_at Decr2 2,4-dienoyl CoA reductase 2, peroxisomal Rn.144598 1371076_at Cyp2b1 cytochrome P450, family 2, subfamily b, polypeptide 1 Rn.91353 1371223_a_at Lepr leptin receptor Rn.9891 1373564_at Hibch 3-hydroxyisobutyryl-Coenzyme A hydrolase Rn.8745 1373778_at --- --- Rn.44359 1375900_at Tnfrsf9 tumor necrosis factor receptor superfamily, member 9 Rn.22307 1376191_at Hpgd hydroxyprostaglandin dehydrogenase 15 (NAD) Rn.6386 1377662_at Pir pirin (iron-binding nuclear protein) Rn.103685 1379275_at Snx10 sorting nexin 10 Rn.44192 1382028_at Pex19 peroxisomal biogenesis factor 19 Rn.203104 1383165_at RGD1310209 similar to KIAA1324 protein Rn.22751 1383585_s_at --- --- --- 1383933_at RGD1308772 similar to KIAA0564 protein Rn.12947 1384580_at C6 complement component 6 Rn.16145 1385574_at RGD1308114 similar to cDNA sequence AF397014 Rn.35332 1386953_at Hsd11b1 hydroxysteroid 11-beta dehydrogenase 1 Rn.888 1386965_at Lpl lipoprotein lipase Rn.3834 1387100_at Aqp3 aquaporin 3 Rn.11109 1387243_at Cyp1a2 cytochrome P450, family 1, subfamily a, polypeptide 2 Rn.5563 1387455_a_at Vldlr very low density lipoprotein receptor Rn.9975 1388199_at Epcam epithelial cell adhesion molecule Rn.106481 1388489_at Ndufa3 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3 Rn.3263 1389611_at Vldlr very low density lipoprotein receptor Rn.9975 1390358_at Cacna2d3 calcium channel, voltage-dependent, alpha2/delta subunit 3 Rn.206369 1390419_a_at Tusc3 tumor suppressor candidate 3 Rn.35146 1390557_at Gca grancalcin Rn.222162 1393933_at Sorl1 sortilin-related receptor, LDLR class A repeats-containing Rn.46267 1394786_at Sorl1 sortilin-related receptor, LDLR class A repeats-containing Rn.46267 1397924_at --- --- Rn.169405 solute carrier family 25 (carnitine/acylcarnitine translocase), member 1398249_at Slc25a20 Rn.3289 20 Supplementary Data 1.(continued) Gene marker sets in each liver toxicity phenotype HCB&PB: 10 probe sets Probe Set ID Gene Symbol Gene Title UniGene ID 1368408_at Grk5 G protein-coupled receptor kinase 5 Rn.6500 1368651_at Pklr pyruvate kinase, liver and RBC Rn.48821 1370828_at Zdhhc2 zinc finger, DHHC-type containing 2 Rn.17310 1372297_at Gsta4 glutathione S-transferase alpha 4 Rn.57528 1377161_at --- --- Rn.34711 1384910_at Lrtm2 leucine-rich repeats and transmembrane domains 2 Rn.34565 1386901_at Cd36 CD36 molecule (thrombospondin receptor) Rn.102418 1387006_at Sult2al1 sulfotransferase family 2A, dehydroepiandrosterone (DHEA)-preferring-like 1 Rn.221887 1388199_at Epcam epithelial cell adhesion molecule Rn.106481 1396035_at Rpesp RPE-spondin Rn.144410 .
Load more

Recommended publications
  • Copper, Lysyl Oxidase, and Extracellular Matrix Protein Cross-Linking1–3
    Copper, lysyl oxidase, and extracellular matrix protein cross-linking1–3 Robert B Rucker, Taru Kosonen, Michael S Clegg, Alyson E Mitchell, Brian R Rucker, Janet Y Uriu-Hare, and Carl L Keen Downloaded from https://academic.oup.com/ajcn/article/67/5/996S/4666210 by guest on 01 October 2021 ABSTRACT Protein-lysine 6-oxidase (lysyl oxidase) is a progress toward understanding copper’s role advanced quickly. cuproenzyme that is essential for stabilization of extracellular Lysyl oxidase is responsible for the formation of lysine-derived matrixes, specifically the enzymatic cross-linking of collagen and cross-links in connective tissue, particularly in collagen and elastin. A hypothesis is proposed that links dietary copper levels elastin. Normal cross-linking is essential in providing resistance to dynamic and proportional changes in lysyl oxidase activity in to elastolysis and collagenolysis by nonspecific proteinases, eg, connective tissue. Although nutritional copper status does not various proteinases involved in blood coagulation (11). Resis- influence the accumulation of lysyl oxidase as protein or lysyl tance to proteolysis occurs within a short period of copper reple- oxidase steady state messenger RNA concentrations, the direct tion in most animals; eg, Tinker et al (12) observed that the depo- influence of dietary copper on the functional activity of lysyl oxi- sition of aortic elastin is restored to near normal values after dase is clear. The hypothesis is based on the possibility that cop- 48–72 h of copper repletion in copper-deficient cockerels. per efflux and lysyl oxidase secretion from cells may share a Effects of copper deprivation are most pronounced in common pathway.
    [Show full text]
  • Downregulation of Lysyl Oxidase and Lysyl Oxidase-Like Protein 2
    Xu et al. Experimental & Molecular Medicine (2019) 51:20 https://doi.org/10.1038/s12276-019-0211-9 Experimental & Molecular Medicine ARTICLE Open Access Downregulation of lysyl oxidase and lysyl oxidase-like protein 2 suppressed the migration and invasion of trophoblasts by activating the TGF-β/collagen pathway in preeclampsia Xiang-Hong Xu 1,YuanhuiJia1,XinyaoZhou1,DandanXie1, Xiaojie Huang1, Linyan Jia1, Qian Zhou1, Qingliang Zheng1, Xiangyu Zhou1,KaiWang1 and Li-Ping Jin1 Abstract Preeclampsia is a pregnancy-specific disorder that is a major cause of maternal and fetal morbidity and mortality with a prevalence of 6–8% of pregnancies. Although impaired trophoblast invasion in early pregnancy is known to be closely associated with preeclampsia, the underlying mechanisms remain elusive. Here we revealed that lysyl oxidase (LOX) and LOX-like protein 2 (LOXL2) play a critical role in preeclampsia. Our results demonstrated that LOX and LOXL2 expression decreased in preeclamptic placentas. Moreover, knockdown of LOX or LOXL2 suppressed trophoblast cell migration and invasion. Mechanistically, collagen production was induced in LOX-orLOXL2-downregulated trophoblast cells through activation of the TGF-β1/Smad3 pathway. Notably, inhibition of the TGF-β1/Smad3 pathway 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; could rescue the defects caused by LOX or LOXL2 knockdown, thereby underlining the significance of the TGF-β1/ Smad3 pathway downstream of LOX and LOXL2 in trophoblast cells. Additionally, induced collagen production and activated TGF-β1/Smad3 were observed in clinical samples from preeclamptic placentas. Collectively, our study suggests that the downregulation of LOX and LOXL2 leading to reduced trophoblast cell migration and invasion through activation of the TGF-β1/Smad3/collagen pathway is relevant to preeclampsia.
    [Show full text]
  • Collagens, Modifying Enzymes and Their Mutations in Humans, Flies And
    Review TRENDS in Genetics Vol.20 No.1 January 2004 33 Collagens, modifying enzymes and their mutations in humans, flies and worms Johanna Myllyharju and Kari I. Kivirikko Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, FIN-90014 Oulu, Finland Collagens and proteins with collagen-like domains form Collagens are the most abundant proteins in the human large superfamilies in various species, and the numbers body, constituting ,30% of its protein mass. The import- of known family members are increasing constantly. ant roles of these proteins have been clearly demonstrated Vertebrates have at least 27 collagen types with 42 dis- by the wide spectrum of diseases caused by a large number tinct polypeptide chains, >20 additional proteins with of mutations found in collagen genes. This article will collagen-like domains and ,20 isoenzymes of various review the collagen superfamilies and their mutations in collagen-modifying enzymes. Caenorhabditis elegans vertebrates, Drosophila melanogaster and the nematode has ,175 cuticle collagen polypeptides and two base- Caenorhabditis elegans. The genomes of these two model ment membrane collagens. Drosophila melanogaster invertebrate species have been fully sequenced, and it is has far fewer collagens than many other species but therefore possible to identify all of the collagen genes has ,20 polypeptides similar to the catalytic subunits present in these species. Because of the extensive of prolyl 4-hydroxylase, the key enzyme of collagen syn- literature in these fields, this review will focus primarily thesis. More than 1300 mutations have so far been on recent advances. More detailed accounts and more characterized in 23 of the 42 human collagen genes complete references can be found in previous reviews, for in various diseases, and many mouse models and example Refs [1–6].
    [Show full text]
  • Discovery and Evaluation of Inhibitor of LARP6 As Specific Antifibrotic
    www.nature.com/scientificreports OPEN Discovery and evaluation of inhibitor of LARP6 as specifc antifbrotic compound Received: 6 August 2018 Branko Stefanovic1, Zarko Manojlovic2, Cynthia Vied 3, Crystal-Dawn Badger3,4 & Accepted: 27 November 2018 Lela Stefanovic1 Published: xx xx xxxx Fibrosis is characterized by excessive production of type I collagen. Biosynthesis of type I collagen in fbrosis is augmented by binding of protein LARP6 to the 5′ stem-loop structure (5′SL), which is found exclusively in type I collagen mRNAs. A high throughput screen was performed to discover inhibitors of LARP6 binding to 5′SL, as potential antifbrotic drugs. The screen yielded one compound (C9) which was able to dissociate LARP6 from 5′ SL RNA in vitro and to inactivate the binding of endogenous LARP6 in cells. Treatment of hepatic stellate cells (liver cells responsible for fbrosis) with nM concentrations of C9 reduced secretion of type I collagen. In precision cut liver slices, as an ex vivo model of hepatic fbrosis, C9 attenuated the profbrotic response at 1 μM. In prophylactic and therapeutic animal models of hepatic fbrosis C9 prevented development of fbrosis or hindered the progression of ongoing fbrosis when administered at 1 mg/kg. Toxicogenetics analysis revealed that only 42 liver genes changed expression after administration of C9 for 4 weeks, suggesting minimal of target efects. Based on these results, C9 represents the frst LARP6 inhibitor with signifcant antifbrotic activity. Fibrosis is characterized by excessive synthesis of type I collagen in various organs and major complications of fbrosis are direct result of massive deposition of type I collagen in the extracellular matrix1,2.
    [Show full text]
  • Fibronectin and Tenascin-C: Accomplices in Vascular Morphogenesis During Development and Tumor Growth ELLEN VAN OBBERGHEN-SCHILLING*,1,2, RICHARD P
    Int. J. Dev. Biol. 55: 511-525 doi: 10.1387/ijdb.103243eo www.intjdevbiol.com Fibronectin and tenascin-C: accomplices in vascular morphogenesis during development and tumor growth ELLEN VAN OBBERGHEN-SCHILLING*,1,2, RICHARD P. TUCKER3, FALK SAUPE4, ISABELLE GASSER4, BOTOND CSEH1,2, GERTRAUD OREND*,4,5,6 1CNRS UMR6543, IBDC, Nice, France, 2University of Nice-Sophia Antipolis, Nice, France, 3Cell Biology and Human Anatomy, University of California at Davis, USA, 4Inserm U682, Strasbourg, France, 5University of Strasbourg, UMR- S682, Strasbourg, France and 6Department of Molecular Biology, CHRU Strasbourg, Strasbourg, France ABSTRACT In addition to soluble factors, the extracellular matrix (ECM) also plays a vital role in normal vasculogenesis and in the pathological angiogenesis of many disease states. Here we will review what is known about the role of the ECM molecules fibronectin and tenascin-C in the vasculature and highlight a potential collaborative interplay between these molecules in develop- mental and tumorigenic angiogenesis. We will address the evolution of these modular proteins, their cellular interactions and how they become assembled into an insoluble matrix that impacts the assembly of other ECM proteins and the bioavailability of pro-angiogenic factors. The role of fibronectin and tenascin-C networks in tumor angiogenesis and metastasis will be described. We will elaborate on lessons learned about their role in vessel function from the functional ablation or the ectopic expression of both molecules. We will also elaborate on potential mechanisms of how fibronectin and tenascin-C affect cell adhesion and signaling that are relevant to angiogenesis. KEY WORDS: tumor angiogenesis, matrix assembly, fibronectin, tenascin-C Introduction blood vessels from preexisting vessels (Risau, 1997).
    [Show full text]
  • Molecular Defects in the Ehlers-Danlos Syndrome
    0022-202X/82/79o:l-090s$02.00/0 THE .JOURNAL OF INVESTIGATIVE DERMATOLOGY, 79:908-92s, 1982 V "I. 7�). Supplement I Copyright © 1!J82 hy The Williams & Wilkins Co. Printed in U.S.A. Molecular Defects in the Ehlers-Danlos Syndrome SHELDON R. PINNELL, M.D. Division of Dermatology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, U.S.A Several abnormalities in collagen biosynthesis have of lysyl hydroxylase. Two mutant enzymes have been charac­ been described in patients with Ehlers-Danlos syndrome. terized. One has an altered affInity for ascorbate and is ther­ Examples of collagen structural mutations as well as mally labile [5]. This apparently represents a structural muta­ post-translational enzymatic defects have been detected. tion of the enzyme. The other enzyme was kinetically normal Patients with hydroxylysine-deficient collagen disease but the activity was markedly diminished [6). This may repre­ (Ehlers-Danlos type VI) have diminished lysyl hydroxy­ sent a structural or regulatory mutation. lase activity. One mutant enzyme has been characterized The relative hydroxylation of tissue collagens has been vari­ which is thermally labile and had an altered affinity for able in this disorder [2, 7]. Although skin was markedly defIcient ascorbate. Another mutant enzyme had a normal re­ in hydroxylysine, bone was less defIcient and cartilage was quirement for cofactors but activity was diminished. normally hydroxylated. The explanation for this variability is Type VII Ehlers-Danlos syndrome is associated with unknown although enzymatic polymorphism has not been ex­ altered processing of procollagen to collagen. Most often cluded. Indeed evidence for isozymes has been reported [8].
    [Show full text]
  • Enhanced Fibrillin-2 Expression Is a General Feature of Wound
    Laboratory Investigation (2010) 90, 739–752 & 2010 USCAP, Inc All rights reserved 0023-6837/10 $32.00 Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-b Ju¨rgen Brinckmann1,2, Nico Hunzelmann3, Birgit Kahle1,Ju¨rgen Rohwedel2, Jan Kramer2,4, Mark A Gibson5, Dirk Hubmacher6 and Dieter P Reinhardt6 Wound healing and sclerosis are characterized by an increase of extracellular matrix proteins, which are characteristically expressed in the embryo–fetal period. We analyzed the expression of fibrillin-2, which is typically found in embryonic tissues, but only scarcely in adult skin. In wound healing and sclerotic skin diseases such as lipodermatosclerosis and scleroderma, a marked increase of fibrillin-2 expression was found by immunohistology. Double labelling of fibrillin-2 and tenascin-C, which is also expressed in wound healing and sclerosis, showed co-localization of both proteins. Solid-phase and slot blot-overlay assays showed a dose-dependent binding of the recombinant N-terminal half of fibrillin-2 (rFBN2-N) to tenascin-C. Real-time PCR showed an increase of the fibrillin-2 gene expression in cell culture triggered by typical mediators for fibroblast activation such as serum, IL-4, and TGF-b. By contrast, prolonged hypoxia is not associated with changes in fibrillin-2 expression. Tenascin-C is an anti-adhesive substrate for fibroblasts, whereas fibrillin-2 stimulates cell attachment. Attachment assays using mixed substrates showed decreased cell attachment when tenascin-C and rFBN2-N were coated together, compared with the attachment to rFBN2-N alone.
    [Show full text]
  • The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by in Vitro Cultured Osteoblasts and Mesenchymal Stem Cells
    cancers Article The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells Elise Aasebø 1 , Even Birkeland 2, Frode Selheim 2, Frode Berven 2, Annette K. Brenner 1 and Øystein Bruserud 1,3,* 1 Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway; [email protected] (E.A.); [email protected] (A.K.B.) 2 The Proteomics Facility of the University of Bergen (PROBE), University of Bergen, N-5021 Bergen, Norway; [email protected] (E.B.); [email protected] (F.S.); [email protected] (F.B.) 3 Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway * Correspondence: [email protected] or [email protected]; Tel.: +47-5597-2997 Simple Summary: Normal blood cells are formed in the bone marrow by a process called hematopoiesis. This process is supported by a network of non-hematopoietic cells including connective tissue cells, blood vessel cells and bone-forming cells. However, these cells can also support the growth of cancer cells, i.e., hematological malignancies (e.g., leukemias) and cancers that arise in another organ and spread to the bone marrow. Two of these cancer-supporting normal cells are bone-forming osteoblasts and a subset of connective tissue cells called mesenchymal stem cells. One mechanism for their cancer support is the release of proteins that support cancer cell proliferation and progression of the cancer disease. Our present study shows that both these normal cells release a wide range of proteins that support cancer cells, and inhibition of this protein-mediated cancer support may become a new strategy for cancer treatment.
    [Show full text]
  • GIP) Directly Affects Collagen fibril Diameter and Collagen Cross-Linking in Osteoblast Cultures
    Bone 74 (2015) 29–36 Contents lists available at ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone Original Full Length Article Glucose-dependent insulinotropic polypeptide (GIP) directly affects collagen fibril diameter and collagen cross-linking in osteoblast cultures Aleksandra Mieczkowska a, Beatrice Bouvard b, Daniel Chappard a,c, Guillaume Mabilleau a,c,⁎ a GEROM Groupe Etudes Remodelage Osseux et bioMatériaux—LHEA, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, LUNAM Université, 49933 Angers Cedex, France b Service de Rhumatologie, CHU d'Angers, 49933 Angers Cedex, France c SCIAM, Service Commun d'Imagerie et Analyses Microscopiques, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, LUNAM Université, 49933 Angers Cedex, France article info abstract Article history: Glucose-dependent insulinotropic polypeptide (GIP) is absolutely crucial in order to obtain optimal bone Received 4 October 2014 strength and collagen quality. However, as the GIPR is expressed in several tissues other than bone, it is difficult Revised 19 December 2014 to ascertain whether the observed modifications of collagen maturity, reported in animal studies, were due to di- Accepted 5 January 2015 rect effects on osteoblasts or indirect through regulation of signals originating from other tissues. The aims of the Available online 10 January 2015 present study were to investigate whether GIP can directly affect collagen biosynthesis and processing in osteo- Edited by Ms. J. Aubin blast cultures and to decipher which molecular pathways were necessary for such effects. MC3T3-E1 cells were cultured in the presence of GIP ranged between 10 and 100 pM. Collagen fibril diameter Keywords: was investigated by electron microscopy whilst collagen maturity was determined by Fourier transform infra- GIP red microspectroscopy (FTIRM).
    [Show full text]
  • Abnormal Copper Metabolism and Deficient Lysyl Oxidase Activity in a Heritable Connective Tissue Disorder
    Abnormal copper metabolism and deficient lysyl oxidase activity in a heritable connective tissue disorder. H Kuivaniemi, … , I Kaitila, K I Kivirikko J Clin Invest. 1982;69(3):730-733. https://doi.org/10.1172/JCI110503. Research Article Biochemical abnormalities were studied in two brothers with bladder divericulas, inguinal hernias, slight skin laxity, and hyperelasticity and skeletal abnormalities including occipital exostoses. Lysyl oxidase activity was low in the medium of cultured skin fibroblasts, this abnormality being accompanied by reduced conversion of the newly synthesized collagen into the soluble form. Copper concentrations were markedly elevated in the cultured skin fibroblasts, but decreased in the serum and hair. Serum cerulophasmin levels were also low. The reduced lysyl oxidase activity is suggested to be responsible for ther clinical manifestations, but the deficiency in this copper-dependent enzyme may be secondary to the abnormalities in the metabolism of the cation. Nevertheless, a mutation directly affecting both lysyl oxidase and an intracellular copper transport protein cannot be excluded. The disease is tentatively classified as one subtype of the Ehlers-Danlos syndrome. Find the latest version: https://jci.me/110503/pdf Abnormal Copper Metabolism and Deficient Lysyl Oxidase Activity in a Heritable Connective Tissue Disorder HELENA KUIVANIEMI, LEENA PELTONEN, AARNO PALOTIE, ILKKA KAITILA, and KARI I. KIvIRIKKO, Departments of Medical Biochemistry and Anatomy, University of Oulu, SF-90220 Oulu 22, Department of Medical Genetics and Children's Hospital, University of Helsinki, SF-00290 Helsinki 29, Finland A B S T R A C T Biochemical abnormalities were stud- ities are probably due to a reduction in the activity of ied in two brothers with bladder divericulas, inguinal lysyl oxidase, a copper-dependent enzyme that initi- hernias, slight skin laxity, and hyperelasticity and skel- ates the cross-linking of collagen and elastin by cata- etal abnormalities including occipital exostoses.
    [Show full text]
  • Lysyl Oxidase Inhibition Via Β- Aminoproprionitrile Hampers Human Umbilical Vein Endothelial Cell Angiogenesis and Migration in Vitro
    Lysyl oxidase inhibition via β- aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Shi, Lin, Ning Zhang, Hetao Liu, Lei Zhao, Jing Liu, Juan Wan, Wenyi Wu, Hetian Lei, Rongqing Liu, and Mei Han. 2018. “Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro.” Molecular Medicine Reports 17 (4): 5029-5036. doi:10.3892/mmr.2018.8508. http://dx.doi.org/10.3892/mmr.2018.8508. Published Version doi:10.3892/mmr.2018.8508 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:35981960 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA MOLECULAR MEDICINE REPORTS 17: 5029-5036, 2018 Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro LIN SHI1*, NING ZHANG1*, HETAO LIU1, LEI ZHAO1, JING LIU1, JUAN WAN2, WENYI WU3, HETIAN LEI3, RONGQING LIU2 and MEI HAN1 1Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University; 2Department of Rheumatology and Immunology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China; 3Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA Received August 13, 2017; Accepted January 17, 2018 DOI: 10.3892/mmr.2018.8508 Abstract.
    [Show full text]
  • Linking LOXL2 to Cardiac Interstitial Fibrosis
    International Journal of Molecular Sciences Review Linking LOXL2 to Cardiac Interstitial Fibrosis Melisse Erasmus 1,2 , Ebrahim Samodien 1 , Sandrine Lecour 3 , Martin Cour 4 , Oscar Lorenzo 5,6 , Phiwayinkosi Dludla 1 , Carmen Pheiffer 1,2 and Rabia Johnson 1,2,* 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7501, South Africa; [email protected] (M.E.); [email protected] (E.S.); [email protected] (P.D.); carmen.pheiff[email protected] (C.P.) 2 Department of Medical Physiology, Stellenbosch University, Cape Town 7505, South Africa 3 Hatter Institute for Cardiovascular Research in Africa (HICRA), University of Cape Town, Cape Town 7925, South Africa; [email protected] 4 Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, Place d’Arsonval, 69437 Lyon, France; [email protected] 5 Institute de Investigación Sanitaria-FJD, Faculty of Medicine, University Autónoma de Madrid, 28049 Madrid, Spain; [email protected] 6 Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Network, 28040 Madrid, Spain * Correspondence: [email protected] Received: 8 July 2020; Accepted: 29 July 2020; Published: 18 August 2020 Abstract: Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications.
    [Show full text]