TITLE Loss-Of-Function Mutations in SERPINB8
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Biomarkers of Neonatal Skin Barrier Adaptation Reveal Substantial Differences Compared to Adult Skin
www.nature.com/pr CLINICAL RESEARCH ARTICLE OPEN Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin Marty O. Visscher1,2, Andrew N. Carr3, Jason Winget3, Thomas Huggins3, Charles C. Bascom3, Robert Isfort3, Karen Lammers1 and Vivek Narendran1 BACKGROUND: The objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2). METHODS: Skin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34–<37 weeks (LPT), and ≥37 weeks (FT). RESULTS: Forty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2. CONCLUSIONS: Neonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the 1234567890();,: barrier antimicrobial properties. -
Propranolol-Mediated Attenuation of MMP-9 Excretion in Infants with Hemangiomas
Supplementary Online Content Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.4773 eTable. List of All of the Proteins Identified by Proteomics This supplementary material has been provided by the authors to give readers additional information about their work. © 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable. List of All of the Proteins Identified by Proteomics Protein Name Prop 12 mo/4 Pred 12 mo/4 Δ Prop to Pred mo mo Myeloperoxidase OS=Homo sapiens GN=MPO 26.00 143.00 ‐117.00 Lactotransferrin OS=Homo sapiens GN=LTF 114.00 205.50 ‐91.50 Matrix metalloproteinase‐9 OS=Homo sapiens GN=MMP9 5.00 36.00 ‐31.00 Neutrophil elastase OS=Homo sapiens GN=ELANE 24.00 48.00 ‐24.00 Bleomycin hydrolase OS=Homo sapiens GN=BLMH 3.00 25.00 ‐22.00 CAP7_HUMAN Azurocidin OS=Homo sapiens GN=AZU1 PE=1 SV=3 4.00 26.00 ‐22.00 S10A8_HUMAN Protein S100‐A8 OS=Homo sapiens GN=S100A8 PE=1 14.67 30.50 ‐15.83 SV=1 IL1F9_HUMAN Interleukin‐1 family member 9 OS=Homo sapiens 1.00 15.00 ‐14.00 GN=IL1F9 PE=1 SV=1 MUC5B_HUMAN Mucin‐5B OS=Homo sapiens GN=MUC5B PE=1 SV=3 2.00 14.00 ‐12.00 MUC4_HUMAN Mucin‐4 OS=Homo sapiens GN=MUC4 PE=1 SV=3 1.00 12.00 ‐11.00 HRG_HUMAN Histidine‐rich glycoprotein OS=Homo sapiens GN=HRG 1.00 12.00 ‐11.00 PE=1 SV=1 TKT_HUMAN Transketolase OS=Homo sapiens GN=TKT PE=1 SV=3 17.00 28.00 ‐11.00 CATG_HUMAN Cathepsin G OS=Homo -
Low P66shc with High Serpinb3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma
biology Article Low P66shc with High SerpinB3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma Silvano Fasolato 1, Mariagrazia Ruvoletto 1 , Giorgia Nardo 2, Andrea Rasola 3, Marco Sciacovelli 3, Giacomo Zanus 4,5, Cristian Turato 6 , Santina Quarta 1 , Liliana Terrin 1, Gian Paolo Fadini 1 , Giulio Ceolotto 1, Maria Guido 1, Umberto Cillo 4,7, Stefano Indraccolo 2,4, Paolo Bernardi 3 and Patrizia Pontisso 1,* 1 Department of Medicine, University of Padua, Via Giustiniani, 2, 35128 Padua, Italy; [email protected] (S.F.); [email protected] (M.R.); [email protected] (S.Q.); [email protected] (L.T.); [email protected] (G.P.F.); [email protected] (G.C.); [email protected] (M.G.) 2 Istituto Oncologico Veneto IOV- IRCCS, 35128 Padua, Italy; [email protected] (G.N.); [email protected] (S.I.) 3 Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy; [email protected] (A.R.); [email protected] (M.S.); [email protected] (P.B.) 4 Department of Surgical, Oncological and Gastroenterological Sciences-DISCOG, University of Padua, 35128 Padua, Italy; [email protected] (G.Z.); [email protected] (U.C.); [email protected] (S.I) 5 Hepatobiliary and Pancreatic Surgery Unit-Treviso Hospital, 31100 Treviso, Italy 6 Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy; [email protected] 7 Unit of Hepatobiliary Surgery and Liver Transplantation, Padua University Hospital, 35128 Padua, Italy * Correspondence: [email protected]; Tel.: +39-049-821-7872; Fax: +39-049-875-4179 Citation: Fasolato, S.; Ruvoletto, M.; Simple Summary: Cell proliferation and escape from apoptosis are important pathological features Nardo, G.; Rasola, A.; Sciacovelli, M.; of hepatocellular carcinoma, one of the tumors with the highest mortality rate worldwide. -
SERPINB3/4 Polyclonal Antibody
PRODUCT DATA SHEET Bioworld Technology,Inc. SERPINB3/4 polyclonal antibody Catalog: BS60990 Host: Rabbit Reactivity: Human,Mouse,Rat BackGround: Swiss-Prot: Metastasis of a primary tumor to a distant site is deter- P29508/P48594 mined through signaling cascades that break down inter- Purification&Purity: actions between the cell and extracellular matrix proteins. The antibody was affinity-purified from rabbit antiserum Among the proteins mediating metastasis are serine by affinity-chromatography using epitope-specific im- prote-ases, such as neutrophil elastase. In 1985, Dr. Jim munogen and the purity is > 95% (by SDS-PAGE). Travis and Dr. R.W. Carrell designated an emerging fam- Applications: ily of serine protease inhibitors as the serpin fam-ily, WB: 1:500~1:1000 which share homology in both primary amino acid se- Storage&Stability: quence and tertiary structure. Serpins contain a stretch of Store at 4°C short term. Aliquot and store at -20°C long peptide that mimics a true substrate for a corresponding term. Avoid freeze-thaw cycles. serine protease. Serine proteases bind to this substrate Specificity: mimic in a 1:1 stoichiometric fashion and become cata- SERPINB3/4 polyclonal antibody detects endogenous lytically inactive. Aberrant ex-pression of serpin family levels of SERPINB3/4 protein. members can contribute to a number of conditions, in- DATA: cluding emphysema (a-1 antitrypsin deficiency), fatal bleeding (elastase to thrombin specificity) and thrombosis (antithrombin deficiency), and are indicators of cancer stage phenotypes (circulating levels of squamous cell car- cinoma antigen, known as SCCA1, increase in advancing stages of some cervical, lung, esophageal and head and neck cancers). -
Differential Gene Expression of Serine Protease Inhibitors in Bovine
Hayashi et al. Reproductive Biology and Endocrinology 2011, 9:72 http://www.rbej.com/content/9/1/72 RESEARCH Open Access Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia Ken-Go Hayashi, Koichi Ushizawa, Misa Hosoe and Toru Takahashi* Abstract Background: SERPINs (serine protease inhibitors) regulate proteases involving fibrinolysis, coagulation, inflammation, cell mobility, cellular differentiation and apoptosis. This study aimed to investigate differentially expressed genes of members of the SERPIN superfamily between healthy and atretic follicles using a combination of microarray and quantitative real-time PCR (QPCR) analysis. In addition, we further determined mRNA and protein localization of identified SERPINs in estradiol (E2)-active and E2-inactive follicles by in situ hybridization and immunohistochemistry. Methods: We performed microarray analysis of healthy (10.7 +/- 0.7 mm) and atretic (7.8 +/- 0.2 mm) follicles using a custom-made bovine oligonucleotide microarray to screen differentially expressed genes encoding SERPIN superfamily members between groups. The expression profiles of six identified SERPIN genes were further confirmed by QPCR analysis. In addition, mRNA and protein localization of four SERPINs was investigated in E2- active and E2-inactive follicles using in situ hybridization and immunohistochemistry. Results: We have identified 11 SERPIN genes expressed in healthy and atretic follicles by microarray analysis. QPCR analysis confirmed that mRNA expression of four SERPINs (SERPINA5, SERPINB6, SERPINE2 and SERPINF2) was greater in healthy than in atretic follicles, while two SERPINs (SERPINE1 and SERPING1) had greater expression in atretic than in healthy follicles. In situ hybridization showed that SERPINA5, SERPINB6 and SERPINF2 mRNA were localized in GCs of E2-active follicles and weakly expressed in GCs of E2-inactive follicles. -
Characterisation of Serpinb2 As a Stress Response Modulator
University of Wollongong Research Online University of Wollongong Thesis Collection 1954-2016 University of Wollongong Thesis Collections 2015 Characterisation of SerpinB2 as a stress response modulator Jodi Anne Lee University of Wollongong Follow this and additional works at: https://ro.uow.edu.au/theses University of Wollongong Copyright Warning You may print or download ONE copy of this document for the purpose of your own research or study. The University does not authorise you to copy, communicate or otherwise make available electronically to any other person any copyright material contained on this site. You are reminded of the following: This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part of this work may be reproduced by any process, nor may any other exclusive right be exercised, without the permission of the author. Copyright owners are entitled to take legal action against persons who infringe their copyright. A reproduction of material that is protected by copyright may be a copyright infringement. A court may impose penalties and award damages in relation to offences and infringements relating to copyright material. Higher penalties may apply, and higher damages may be awarded, for offences and infringements involving the conversion of material into digital or electronic form. Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong. Recommended Citation Lee, Jodi Anne, Characterisation of SerpinB2 as a stress response modulator, Doctor of Philosophy thesis, School of Biological Sciences, University of Wollongong, 2015. https://ro.uow.edu.au/theses/4538 Research Online is the open access institutional repository for the University of Wollongong. -
Adaptive Evolution and Divergence of SERPINB3: a Young Duplicate in Great Apes
Adaptive Evolution and Divergence of SERPINB3: A Young Duplicate in Great Apes Sı´lvia Gomes1*, Patrı´cia I. Marques1,2, Rune Matthiesen3, Susana Seixas1* 1 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal, 2 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal, 3 National Health Institute Doutor Ricardo Jorge (INSA), Lisboa, Portugal Abstract A series of duplication events led to an expansion of clade B Serine Protease Inhibitors (SERPIN), currently displaying a large repertoire of functions in vertebrates. Accordingly, the recent duplicates SERPINB3 and B4 located in human 18q21.3 SERPIN cluster control the activity of different cysteine and serine proteases, respectively. Here, we aim to assess SERPINB3 and B4 coevolution with their target proteases in order to understand the evolutionary forces shaping the accelerated divergence of these duplicates. Phylogenetic analysis of primate sequences placed the duplication event in a Hominoidae ancestor (,30 Mya) and the emergence of SERPINB3 in Homininae (,9 Mya). We detected evidence of strong positive selection throughout SERPINB4/B3 primate tree and target proteases, cathepsin L2 (CTSL2) and G (CTSG) and chymase (CMA1). Specifically, in the Homininae clade a perfect match was observed between the adaptive evolution of SERPINB3 and cathepsin S (CTSS) and most of sites under positive selection were located at the inhibitor/protease interface. Altogether our results seem to favour a coevolution hypothesis for SERPINB3, CTSS and CTSL2 and for SERPINB4 and CTSG and CMA1.A scenario of an accelerated evolution driven by host-pathogen interactions is also possible since SERPINB3/B4 are potent inhibitors of exogenous proteases, released by infectious agents. -
Pso P27, a SERPINB3/B4-Derived Protein, Is Most Likely a Common Autoantigen in Chronic Inflammatory Diseases
Clinical Immunology 174 (2017) 10–17 Contents lists available at ScienceDirect Clinical Immunology journal homepage: www.elsevier.com/locate/yclim Pso p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in chronic inflammatory diseases Ole-Jan Iversen a,⁎,HildeLysvanda, Geir Slupphaug b a Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway b Department of Cancer Research and Molecular Medicine, Faculty of Medicine and PROMEC Core Facility for Proteomics and Metabolomics, Norwegian University of Science and Technology, NTNU, Trondheim, Norway article info abstract Article history: Autoimmune diseases are characterized by chronic inflammatory reactions localized to an organ or organ- Received 17 October 2016 system. They are caused by loss of immunologic tolerance toward self-antigens, causing formation of autoanti- Received in revised form 1 November 2016 bodies that mistakenly attack their own body. Psoriasis is a chronic inflammatory autoimmune skin disease in accepted with revision 13 November 2016 which the underlying molecular mechanisms remain elusive. In this review, we present evidence accumulated Available online 15 November 2016 through more than three decades that the serpin-derived protein Pso p27 is an autoantigen in psoriasis and prob- ably also in other chronic inflammatory diseases. Keywords: Autoimmune diseases Pso p27 is derived from the serpin molecules SERPINB3 and SERPINB4 through non-canonical cleavage by mast Pso p27 cell chymase. In psoriasis, it is exclusively found in skin lesions and not in uninvolved skin. The serpins are cleaved SERPINB3/B4 into three fragments that remain associated as a Pso p27 complex with novel immunogenic properties and in- Mast cells creased tendency to form large aggregates compared to native SERPINB3/B4. -
Serpins—From Trap to Treatment
MINI REVIEW published: 12 February 2019 doi: 10.3389/fmed.2019.00025 SERPINs—From Trap to Treatment Wariya Sanrattana, Coen Maas and Steven de Maat* Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands Excessive enzyme activity often has pathological consequences. This for example is the case in thrombosis and hereditary angioedema, where serine proteases of the coagulation system and kallikrein-kinin system are excessively active. Serine proteases are controlled by SERPINs (serine protease inhibitors). We here describe the basic biochemical mechanisms behind SERPIN activity and identify key determinants that influence their function. We explore the clinical phenotypes of several SERPIN deficiencies and review studies where SERPINs are being used beyond replacement therapy. Excitingly, rare human SERPIN mutations have led us and others to believe that it is possible to refine SERPINs toward desired behavior for the treatment of enzyme-driven pathology. Keywords: SERPIN (serine proteinase inhibitor), protein engineering, bradykinin (BK), hemostasis, therapy Edited by: Marvin T. Nieman, Case Western Reserve University, United States INTRODUCTION Reviewed by: Serine proteases are the “workhorses” of the human body. This enzyme family is conserved Daniel A. Lawrence, throughout evolution. There are 1,121 putative proteases in the human body, and about 180 of University of Michigan, United States Thomas Renne, these are serine proteases (1, 2). They are involved in diverse physiological processes, ranging from University Medical Center blood coagulation, fibrinolysis, and inflammation to immunity (Figure 1A). The activity of serine Hamburg-Eppendorf, Germany proteases is amongst others regulated by a dedicated class of inhibitory proteins called SERPINs Paulo Antonio De Souza Mourão, (serine protease inhibitors). -
Suppression of the Invasion and Migration of Cancer Cells by SERPINB Family Genes and Their Derived Peptides
238 ONCOLOGY REPORTS 27: 238-245, 2012 Suppression of the invasion and migration of cancer cells by SERPINB family genes and their derived peptides RUEY-HWANG CHOU1-4, HUI-CHIN WEN1,7, WEI-GUANG LIANG1,5, SHENG-CHIEH LIN1,5, HSIAO-WEI YUAN1, CHENG-WEN WU1,5,6 and WUN-SHAING WAYNE CHANG1 1National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053; 2Center for Molecular Medicine, China Medical University Hospital, Taichung 40402; 3China Medical University, Taichung 40402; 4Department of Biotechnology, Asia University, Taichung 41354; 5College of Life Science, National Tsing Hua University, Hsinchu 30013; 6Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, Taiwan, R.O.C. Received June 28, 2011; Accepted August 17, 2011 DOI: 10.3892/or.2011.1497 Abstract. Apart from SERPINB2 and SERPINB5, the roles SERPINB RCL-peptides may provide a reasonable strategy of the remaining 13 members of the human SERPINB family against lethal cancer metastasis. in cancer metastasis are still unknown. In the present study, we demonstrated that most of these genes are differentially Introduction expressed in tumor tissues compared to matched normal tissues from lung or breast cancer patients. Overexpression of Cancer metastasis is the leading cause of morbidity and each SERPINB gene effectively suppressed the invasiveness mortality in cancer patients. It is a highly complex process, and motility of malignant cancer cells. Among all of the genes, including cell detachment, migration, invasion, circulation in the SERPINB1, SERPINB5 and SERPINB7 genes were more blood vessels, adhesion, colonization at other sites and forma- potent, and the inhibitory effect was further enhanced by tion of secondary tumors (1). -
Correlation of Serpin–Protease Expression by Comparative Analysis of Real-Time PCR Profiling Data
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Genomics 88 (2006) 173–184 www.elsevier.com/locate/ygeno Correlation of serpin–protease expression by comparative analysis of real-time PCR profiling data Sunita Badola a, Heidi Spurling a, Keith Robison a, Eric R. Fedyk a, Gary A. Silverman b, ⁎ Jochen Strayle c, Rosana Kapeller a,1, Christopher A. Tsu a, a Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139, USA b Department of Pediatrics, University of Pittsburgh School of Medicine, Magee-Women’s Hospital, 300 Halket Street, Pittsburgh, PA 15213, USA c Bayer HealthCare AG, 42096 Wuppertal, Germany Received 2 December 2005; accepted 27 March 2006 Available online 18 May 2006 Abstract Imbalanced protease activity has long been recognized in the progression of disease states such as cancer and inflammation. Serpins, the largest family of endogenous protease inhibitors, target a wide variety of serine and cysteine proteases and play a role in a number of physiological and pathological states. The expression profiles of 20 serpins and 105 serine and cysteine proteases were determined across a panel of normal and diseased human tissues. In general, expression of serpins was highly restricted in both normal and diseased tissues, suggesting defined physiological roles for these protease inhibitors. A high correlation in expression for a particular serpin–protease pair in healthy tissues was often predictive of a biological interaction. The most striking finding was the dramatic change observed in the regulation of expression between proteases and their cognate inhibitors in diseased tissues. -
BMC Genomics Biomed Central
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central BMC Genomics BioMed Central Research article Open Access Analysis of vertebrate genomes suggests a new model for clade B serpin evolution Dion Kaiserman and Phillip I Bird* Address: Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria, Australia Email: Dion Kaiserman - [email protected]; Phillip I Bird* - [email protected] * Corresponding author Published: 23 November 2005 Received: 16 September 2005 Accepted: 23 November 2005 BMC Genomics 2005, 6:167 doi:10.1186/1471-2164-6-167 This article is available from: http://www.biomedcentral.com/1471-2164/6/167 © 2005 Kaiserman and Bird; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The human genome contains 13 clade B serpin genes at two loci, 6p25 and 18q21. The three genes at 6p25 all conform to a 7-exon gene structure with conserved intron positioning and phasing, however, at 18q21 there are two 7-exon genes and eight genes with an additional exon yielding an 8-exon structure. Currently, it is not known how these two loci evolved, nor which gene structure arose first – did the 8-exon genes gain an exon, or did the 7-exon genes lose one? Here we use the genomes of diverse vertebrate species to plot the emergence of clade B serpin genes and to identify the point at which the two genomic structures arose.