Adamtss, Potentially Multifunctional Metalloproteinases of the ADAM Family
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Human ADAM12 Quantikine ELISA
Quantikine® ELISA Human ADAM12 Immunoassay Catalog Number DAD120 For the quantitative determination of A Disintegrin And Metalloproteinase domain- containing protein 12 (ADAM12) concentrations in cell culture supernates, serum, plasma, and urine. This package insert must be read in its entirety before using this product. For research use only. Not for use in diagnostic procedures. TABLE OF CONTENTS SECTION PAGE INTRODUCTION .....................................................................................................................................................................1 PRINCIPLE OF THE ASSAY ...................................................................................................................................................2 LIMITATIONS OF THE PROCEDURE .................................................................................................................................2 TECHNICAL HINTS .................................................................................................................................................................2 MATERIALS PROVIDED & STORAGE CONDITIONS ...................................................................................................3 OTHER SUPPLIES REQUIRED .............................................................................................................................................3 PRECAUTIONS .........................................................................................................................................................................4 -
ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease
International Journal of Molecular Sciences Review ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease Francesca Tosetti 1,* , Massimo Alessio 2, Alessandro Poggi 1,† and Maria Raffaella Zocchi 3,† 1 Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico S. Martino Largo R. Benzi 10, 16132 Genoa, Italy; [email protected] 2 Proteome Biochemistry, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; [email protected] 3 Division of Immunology, Transplants and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work as last author. Abstract: Enzymes, once considered static molecular machines acting in defined spatial patterns and sites of action, move to different intra- and extracellular locations, changing their function. This topological regulation revealed a close cross-talk between proteases and signaling events involving post-translational modifications, membrane tyrosine kinase receptors and G-protein coupled recep- tors, motor proteins shuttling cargos in intracellular vesicles, and small-molecule messengers. Here, we highlight recent advances in our knowledge of regulation and function of A Disintegrin And Metalloproteinase (ADAM) endopeptidases at specific subcellular sites, or in multimolecular com- plexes, with a special focus on ADAM10, and tumor necrosis factor-α convertase (TACE/ADAM17), since these two enzymes belong to the same family, share selected substrates and bioactivity. We will discuss some examples of ADAM10 activity modulated by changing partners and subcellular compartmentalization, with the underlying hypothesis that restraining protease activity by spatial Citation: Tosetti, F.; Alessio, M.; segregation is a complex and powerful regulatory tool. -
Role and Regulation of the Metalloproteinase ADAM8 in Liver Inflammation and Hepatocellular Carcinoma
Role and Regulation of the Metalloproteinase ADAM8 in Liver Inflammation and Hepatocellular Carcinoma Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der RWTH Aachen University zur Erlangung des akademischen Grades einer Doktorin der Naturwissenschaften genehmigte Dissertation vorgelegt von Tanzeela Awan M. Phil Pharmacology aus Layyah, Pakistan Berichter: Herr Universitätsprofessor Dr. rer. nat. Andreas Ludwig Frau Universitätsprofessorin Dr. phil. nat. Gabriele Pradel Herr Universitätsprofessor Dr. rer. nat. Martin Zenke Tag der mündlichen Prüfung: 11.01.2021 Diese Dissertation ist auf den Internetseiten der Universitätsbibliothek online verfügbar. Table of Contents Table of Contents 1 Introduction .......................................................................................... 1 1.1 The Liver .............................................................................................. 1 1.1.1 Cells of the liver ................................................................................... 1 1.1.2 Liver inflammation ............................................................................... 3 1.1.3 Liver carcinoma .................................................................................... 6 1.1.4 Integrin and focal adhesion kinase signalling ...................................... 7 1.2 Metalloproteinases ................................................................................ 9 1.2.1 ADAM proteases: structure and functions of different domains ....... 10 1.3 ADAM8 ............................................................................................. -
ADAMTS13 and 15 Are Not Regulated by the Full Length and N‑Terminal Domain Forms of TIMP‑1, ‑2, ‑3 and ‑4
BIOMEDICAL REPORTS 4: 73-78, 2016 ADAMTS13 and 15 are not regulated by the full length and N‑terminal domain forms of TIMP‑1, ‑2, ‑3 and ‑4 CENQI GUO, ANASTASIA TSIGKOU and MENG HUEE LEE Department of Biological Sciences, Xian Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, P.R. China Received June 29, 2015; Accepted July 15, 2015 DOI: 10.3892/br.2015.535 Abstract. A disintegrin and metalloproteinase with thom- proteolysis activities associated with arthritis, morphogenesis, bospondin motifs (ADAMTS) 13 and 15 are secreted zinc angiogenesis and even ovulation [as reviewed previously (1,2)]. proteinases involved in the turnover of von Willebrand factor Also known as the VWF-cleaving protease, ADAMTS13 and cancer suppression. In the present study, ADAMTS13 is noted for its ability in cleaving and reducing the size of the and 15 were subjected to inhibition studies with the full-length ultra-large (UL) form of the VWF. Reduction in ADAMTS13 and N-terminal domain forms of tissue inhibitor of metallo- activity from either hereditary or acquired deficiency causes proteinases (TIMPs)-1 to -4. TIMPs have no ability to inhibit accumulation of UL-VWF multimers, platelet aggregation and the ADAMTS proteinases in the full-length or N-terminal arterial thrombosis that leads to fatal thrombotic thrombocy- domain form. While ADAMTS13 is also not sensitive to the topenic purpura [as reviewed previously (1,3)]. By contrast, hydroxamate inhibitors, batimastat and ilomastat, ADAMTS15 ADAMTS15 is a potential tumor suppressor. Only a limited app can be effectively inhibited by batimastat (Ki 299 nM). In number of in-depth investigations have been carried out on the conclusion, the present results indicate that TIMPs are not the enzyme; however, expression and profiling studies have shown regulators of these two ADAMTS proteinases. -
ADAM9: a Novel Player in Vestibular Schwannoma Pathogenesis
1856 ONCOLOGY LETTERS 19: 1856-1864, 2020 ADAM9: A novel player in vestibular schwannoma pathogenesis MARIA BREUN1, ALEXANDRA SCHWERDTFEGER1, DONATO DANIEL MARTELLOTTA1, ALMUTH F. KESSLER1, CAMELIA M. MONORANU2, CORDULA MATTHIES1, MARIO LÖHR1* and CARSTEN HAGEMANN1* 1Department of Neurosurgery, University Hospital Würzburg; 2Department of Neuropathology, Institute of Pathology, University of Würzburg, D-97080 Würzburg, Germany Received April 27, 2019; Accepted October 2, 2019 DOI: 10.3892/ol.2020.11299 Abstract. A disintegrin and metalloproteinase 9 (ADAM9) is VS samples (n=60). A total of 30 of them were from patients a member of the transmembrane ADAM family. It is expressed with neurofibromatosis. Healthy peripheral nerves from in different types of solid cancer and promotes tumor invasive- autopsies (n=10) served as controls. ADAM9 mRNA levels ness. To the best of our knowledge, the present study was the were measured by PCR, and protein levels were determined first to examine ADAM9 expression in vestibular schwan- by immunohistochemistry (IHC) and western blotting (WB). nomas (VS) from patients with and without neurofibromatosis The Hannover Classification was used to categorize tumor type 2 (NF2) and to associate the data with clinical parameters extension and hearing loss. ADAM9 mRNA levels were of the patients. The aim of the present study was to evaluate 8.8-fold higher in VS compared with in controls. The levels if ADAM9 could be used as prognostic marker or therapeutic were 5.6-fold higher in patients with NF2 and 12-fold higher in target. ADAM9 mRNA and protein levels were measured in patients with sporadic VS. WB revealed two mature isoforms of the protein, and according to IHC ADAM9 was mainly expressed by S100-positive Schwann cells. -
Importance of Β-APP, ADAM9, 10, 17 in Alzheimer Disease
Available online at www.ijmrhs.com al R edic ese M a of rc l h a & n r H u e o a J l l t h International Journal of Medical Research & a n S ISSN No: 2319-5886 o c i t i Health Sciences, 2019, 8(7): 68-7 e a n n c r e e t s n I • • I J M R H S Importance of β-APP, ADAM9, 10, 17 in Alzheimer Disease: Preliminary Autopsy Study with Immunohistochemical Expression in Human Brain Filiz Eren1, Nursel Turkmen Inanır1,2, Recep Fedakar2, Bulent Eren3*, Murat Serdar Gurses1, Mustafa Numan Ural4, Sumeyya Akyol5, Busra Aynekin5 and Kadir Demircan5 1 Bursa Morgue Department, Council of Forensic Medicine of Turkey, Bursa, Turkey 2 Department of Forensic Medicine, School of Medicine, Uludag University, Bursa, Turkey 5 3 Department of Forensic Medicine, School of Medicine, Tokat Gaziosmanpaşa University Tokat, Turkey 4 5 Bilgemed Work Safety and Security, Bursa, Turkey 5 Independent Researcher, Ankara, Turkey *Corresponding e-mail: [email protected] ABSTRACT Alzheimer’s disease (AD) is encountered as an important health problem. It was exposed that in the pathophysiology of AD, formation, and aggregation of amyloid β from amyloid precursor protein ( APP), was restrained by α-secretase group, ADAM (a disintegrin and metalloproteinase) enzymes. From this perspective, ADAM group of enzymes can be presumably used in the future both as a diagnostic marker, and potential treatment modality. In our study, 9 cases with or without AD in different age groups with various causes of death who were autopsied in the Bursa Morgue Department of the Council of Forensic Medicine of Turkey were included in the study. -
Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes. -
The Positive Side of Proteolysis in Alzheimer's Disease
Hindawi Publishing Corporation Biochemistry Research International Volume 2011, Article ID 721463, 13 pages doi:10.1155/2011/721463 Review Article Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer’s Disease Mallory Gough, Catherine Parr-Sturgess, and Edward Parkin Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK Correspondence should be addressed to Edward Parkin, [email protected] Received 17 August 2010; Accepted 7 September 2010 Academic Editor: Simon J. Morley Copyright © 2011 Mallory Gough et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Alzheimer’s disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (Aβ-)peptides in the brain causing progressive neuronal death. Aβ-peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to this detrimental “amyloidogenic” form of proteolysis, a range of zinc metalloproteinases can process APP via an alternative “nonamyloidogenic” pathway in which the protein is cleaved within its Aβ region thereby precluding the formation of intact Aβ-peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed Aβ-peptides. As such, the zinc metalloproteinases, collectively, are key to downregulating Aβ generation and enhancing its degradation. It is the role of zinc metalloproteinases in this “positive side of proteolysis in Alzheimer’s disease” that is discussed in the current paper. 1. Introduction of 38–43 amino acid peptides called amyloid beta (Aβ)- peptides. -
Effect of Inhibition of Matrix Metalloproteinases on Endometrial Decidualization and Implantation in Mated Rats M
Effect of inhibition of matrix metalloproteinases on endometrial decidualization and implantation in mated rats M. P. Rechtman, J. Zhang and L. A. Salamonsen Prince Henry's Institute ofMedical Research, PO Box 5152, Clayton, Victoria 3168, Australia Implantation of the embryo into the endometrium is a highly regulated event that is critical for establishment of pregnancy. Molecules involved in this process provide potential targets for post-coital contraception. The aims of this study were to determine whether matrix metalloproteinases (MMPs) are present at implantation sites in rats and whether administration of a broad-based inhibitor of MMPs could inhibit embryo implantation. Uterine extracts from non-pregnant rats and from rats on days 3\p=n-\9 of pregnancy were examined for the presence of MMPs. Doxycycline (5 or 15 mg day\m=-\1) was administered by gavage to rats from the day of mating (day 0) to day 7 of pregnancy and the uterus was examined for implantation sites. A number of MMPs were present in all uterine samples. MMP-2 reached a peak on day 3, whereas the highest expression of MMP-7 occurred on day 7. MMP-13 and MMP-3 were present in smaller amounts. MMP-9 was detectable only on day 9. Treatment of rats with doxycycline had no effect on the number of implantation sites or on the total uterine mass. However, in treated rats, the process of decidualization was impaired and both the width and length of the decidual zone was reduced, resulting in a decrease in total decidual area from 1.20 \m=+-\0.07 to 0.91 \m=+-\0.07 mm2 (mean \m=+-\sem, controls versus doxycycline treated, P < 0.02). -
Selective Inhibition of ADAM12 Catalytic Activity Through
Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of metalloproteinases (TIMP)-2 Marie Kveiborg, Jonas Jacobsen, Meng-Huee Lee, Hideaki Nagase, Ulla M Wewer, Gillian Murphy To cite this version: Marie Kveiborg, Jonas Jacobsen, Meng-Huee Lee, Hideaki Nagase, Ulla M Wewer, et al.. Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of metalloproteinases (TIMP)-2. Biochemical Journal, Portland Press, 2010, 430 (1), pp.79-86. 10.1042/BJ20100649. hal-00506526 HAL Id: hal-00506526 https://hal.archives-ouvertes.fr/hal-00506526 Submitted on 28 Jul 2010 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Biochemical Journal Immediate Publication. Published on 10 Jun 2010 as manuscript BJ20100649 Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of metalloproteinases (TIMP)-2 Marie Kveiborg*,§, Jonas Jacobsen*,§, Meng-Huee Lee†, Hideaki Nagase‡, Ulla M. Wewer*,¶, and Gillian Murphy†,¶ *Department of Biomedical Sciences and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark †Department of Oncology, Cambridge University, Cancer Research Institute, Li Ka Shing Centre, Cambridge CB2 ORE, UK ‡Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 65 Aspenlea Road, London W6 8LH, UK §,¶These authors contributed equally to the study. -
Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: the Positive Side of Proteolysis in Alzheimer’S Disease
Hindawi Publishing Corporation Biochemistry Research International Volume 2011, Article ID 721463, 13 pages doi:10.1155/2011/721463 Review Article Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer’s Disease Mallory Gough, Catherine Parr-Sturgess, and Edward Parkin Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK Correspondence should be addressed to Edward Parkin, [email protected] Received 17 August 2010; Accepted 7 September 2010 Academic Editor: Simon J. Morley Copyright © 2011 Mallory Gough et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Alzheimer’s disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (Aβ-)peptides in the brain causing progressive neuronal death. Aβ-peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to this detrimental “amyloidogenic” form of proteolysis, a range of zinc metalloproteinases can process APP via an alternative “nonamyloidogenic” pathway in which the protein is cleaved within its Aβ region thereby precluding the formation of intact Aβ-peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed Aβ-peptides. As such, the zinc metalloproteinases, collectively, are key to downregulating Aβ generation and enhancing its degradation. It is the role of zinc metalloproteinases in this “positive side of proteolysis in Alzheimer’s disease” that is discussed in the current paper. 1. Introduction of 38–43 amino acid peptides called amyloid beta (Aβ)- peptides. -
Original Article Tetraspanin CD9 Interacts with Α-Secretase to Enhance Its Oncogenic Function in Pancreatic Cancer
Am J Transl Res 2020;12(9):5525-5537 www.ajtr.org /ISSN:1943-8141/AJTR0105976 Original Article Tetraspanin CD9 interacts with α-secretase to enhance its oncogenic function in pancreatic cancer Weiwei Lu1*, Aihua Fei1*, Ying Jiang2, Liang Chen1, Yunkun Wang2 1Department of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, PR China; 2Department of Neurosurgery, Shanghai Changzheng Hospital Affiliated to Shanghai Second Military Medical University, 415 Feng Yang Rd, Shanghai 200003, PR China. *Equal contributors. Received December 5, 2019; Accepted June 6, 2020; Epub September 15, 2020; Published September 30, 2020 Abstract: Pancreatic cancer is one of the most lethal cancers and its prognosis remains poor. ADAM family proteins like ADAM10, ADAM9 and ADAM17 function as α-secretase to cleavage cell surface proteins like Notch to facilitate oncogenesis in various tumors. The oncogenic roles of α-secretase in PDAC have been demonstrated but it remains unknown that whether and how α-secretase is regulated in PDAC. Here, we report that the expression of tetraspanin CD9 was increased and strongly associated with poor prognosis in PDAC. CD9 expression was positively associated with α-secretase activity in PDAC tissues and CD9 knock-down inhibited α-secretase activity in PDAC cell lines. Co-immunoprecipitation and GST pull down demonstrates that CD9 directly interacted with ADAM10, ADAM9 and ADAM17, respectively. Cell surface biotin labeling and immunostaining of tagged ADAM proteins show that CD9 promoted cell surface trafficking of ADAM family proteins. In addition, the antibody targeting extracellular domain of CD9 disrupted the interactions between CD9 and ADAM family proteins, reduced cell surface trafficking of ADAM proteins and inhibited α-secretase activity.