Identification of the Membrane-Type Matrix Metalloproteinase MT1-MMP
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MATRIX METALLOPROTEINASE REQUIREMENTS for NEUROMUSCULAR SYNAPTOGENESIS by Mary Lynn Dear Dissertation Submitted to the Faculty O
MATRIX METALLOPROTEINASE REQUIREMENTS FOR NEUROMUSCULAR SYNAPTOGENESIS By Mary Lynn Dear Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biological Sciences January 31, 2018 Nashville, Tennessee Approved: Todd Graham, Ph.D. Kendal Broadie, Ph.D. Katherine Friedman, Ph.D. Barbara Fingleton, Ph.D. Jared Nordman, Ph.D. Copyright © 2018 by Mary Lynn Dear All Rights Reserved ACKNOWLEDGEMENTS I would like to acknowledge my advisor, Kendal Broadie, and the entire Broadie laboratory, both past and present, for their endless support, engaging conversations, thoughtful suggestions and constant encouragement. I would also like to thank my committee members both past and present for playing such a pivotal role in my graduate career and growth as a scientist. I thank the Department of Biological Sciences for fostering my graduate education. I thank the entire protease community for their continued support, helpful suggestions and collaborative efforts that helped my project move forward. I would like to acknowledge Dr. Andrea Page-McCaw and her entire laboratory for helpful suggestions, being engaged in my studies and providing many tools that were invaluable to my project. I thank my parents, Leisa Justus and Raymond Dear, my brother Jake Dear and my best friend Jenna Kaufman. Words cannot describe how grateful I am for your support and encouragement. Most importantly, I would like to thank my husband, Jeffrey Thomas, for always believing in me, your unwavering support and for helping me endure all the ups and downs that come with graduate school. -
What Are the Roles of Metalloproteinases in Cartilage and Bone Damage? G Murphy, M H Lee
iv44 Ann Rheum Dis: first published as 10.1136/ard.2005.042465 on 20 October 2005. Downloaded from REPORT What are the roles of metalloproteinases in cartilage and bone damage? G Murphy, M H Lee ............................................................................................................................... Ann Rheum Dis 2005;64:iv44–iv47. doi: 10.1136/ard.2005.042465 enzyme moiety into an upper and a lower subdomain. A A role for metalloproteinases in the pathological destruction common five stranded beta-sheet and two alpha-helices are in diseases such as rheumatoid arthritis and osteoarthritis, always found in the upper subdomain with a further C- and the irreversible nature of the ensuing cartilage and bone terminal helix in the lower subdomain. The catalytic sites of damage, have been the focus of much investigation for the metalloproteinases, especially the MMPs, have been several decades. This has led to the development of broad targeted for the development of low molecular weight spectrum metalloproteinase inhibitors as potential therapeu- synthetic inhibitors with a zinc chelating moiety. Inhibitors tics. More recently it has been appreciated that several able to fully differentiate between individual enzymes have families of zinc dependent proteinases play significant and not been identified thus far, although a reasonable level of varied roles in the biology of the resident cells in these tissues, discrimination is now being achieved in some cases.7 Each orchestrating development, remodelling, and subsequent family does, however, have other unique domains with pathological processes. They also play key roles in the numerous roles, including the determination of physiological activity of inflammatory cells. The task of elucidating the substrate specificity, ECM, or cell surface localisation (fig 1). -
Microrna-145 Overexpression Attenuates Apoptosis and Increases Matrix Synthesis in Nucleus Pulposus Cells T
Life Sciences 221 (2019) 274–283 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie MicroRNA-145 overexpression attenuates apoptosis and increases matrix synthesis in nucleus pulposus cells T Jie Zhoua,1, Jianchao Sunb,c,1, Dessislava Z. Markovad, Shuangxing Lib,c, Christopher K. Keplerd, ⁎ ⁎⁎ Junmin Hongb,c, Yingjie Huangb,e, Weijian Chene, Kang Xub,f, Fuxin Weig, , Wei Yeb,c, a Department of Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China b Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China c Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China d Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, USA e Department of Orthopedics, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China f Experimental Center of Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China g Department of Orthopedics, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China ARTICLE INFO ABSTRACT Keywords: Aims: Lower back pain is often associated with intervertebral disc degeneration (IDD), which results from a Intervertebral disc degeneration decrease in nucleus pulposus (NP) cells and an imbalance between the degradation and synthesis of extracellular Nucleus pulposus matrix (ECM) components. Multiple microRNAs play crucial roles in the modulation of NP cell apoptosis and microRNA-145 matrix degradation. miR-145 is an important microRNA related to degenerative diseases such as osteoarthritis. Apoptosis Here, the effect of miR-145 in IDD was elucidated. -
Repression of Anti-Proliferative Factor Tob1 in Osteoarthritic Cartilage
Available online http://arthritis-research.com/content/7/2/R274 ResearchVol 7 No 2 article Open Access Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage Mathias Gebauer1*, Joachim Saas2*, Jochen Haag3, Uwe Dietz2, Masaharu Takigawa4, Eckart Bartnik2 and Thomas Aigner3 1Aventis Pharma Deutschland, Functional Genomics, Sanofi-Aventis, Frankfurt, Germany 2Sanofi-Aventis, Disease Group Thrombotic Diseases/Degenerative Joint Diseases, Frankfurt, Germany 3Osteoarticular and Arthritis Research, Department of Pathology, University of Erlangen-Nürnberg, Germany 4Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan * Contributed equally Corresponding author: Thomas Aigner, [email protected] Received: 10 Aug 2004 Revisions requested: 1 Oct 2004 Revisions received: 22 Oct 2004 Accepted: 19 Nov 2004 Published: 11 Jan 2005 Arthritis Res Ther 2005, 7:R274-R284 (DOI 10.1186/ar1479)http://arthritis-research.com/content/7/2/R274 © 2005 Gebauer et al.; 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 Osteoarthritis is the most common degenerative disorder of the genes were detected between normal and osteoarthritic modern world. However, many basic cellular features and cartilage (P < 0.01). One of the significantly repressed genes, molecular processes of the disease are poorly understood. In Tob1, encodes a protein belonging to a family involved in the present study we used oligonucleotide-based microarray silencing cells in terms of proliferation and functional activity. -
Pronase Kit Pretreatment Reagent 901-PRT957-081017
Carezyme III: Pronase Kit Pretreatment Reagent 901-PRT957-081017 Catalog Number: PRT957 KH Description: 25 ml, ready-to-use Intended Use: stored under conditions other than those specified in the package For In Vitro Diagnostic Use insert, they must be verified by the user. Diluted reagents should be Carezyme III: Pronase Kit is a concentrated solution of pronase used promptly; any remaining reagent should be stored at 2ºC to 8ºC. enzyme and accompanying buffer intended for use as a pretreatment Troubleshooting: step on formalin-fixed, paraffin-embedded (FFPE) tissues in Follow the antibody specific protocol recommendations according to immunohistochemistry (IHC) and in situ hybridization (ISH) data sheet provided. If atypical results occur, contact Biocare's procedures. The clinical interpretation of any staining or its absence Technical Support at 1-800-542-2002. should be complemented by morphological studies and proper controls Protocol Recommendations: and should be evaluated within the context of the patient's clinical Deparaffinize tissues and hydrate to water. If necessary perform a history and other diagnostic tests by a qualified pathologist. hydrogen peroxide block, wash in water, and rinse in PBS or TBS. The Summary and Explanation: tissue section is ready for protease digestion. Pronase (Streptomyces griseus) is a commonly used digestive enzyme. Manual IHC: In formalinfixed paraffin-embedded tissues, certain antibody or in situ 1. Combine 1 part Pronase concentrate with 4 parts buffer (0.1%). hybridization probes require enzyme pretreatment for proper Incubate for 5-10 minutes at 37ºC. (Strong) immunohistochemical or in situ hybridization staining. CAREZYME III is 2. Combine 1 part Pronase concentrate with 9 parts buffer (0.05%). -
ADAM17 Targets MMP-2 and MMP-9 Via EGFR-MEK-ERK Pathway Activation to Promote Prostate Cancer Cell Invasion
1714 INTERNATIONAL JOURNAL OF ONCOLOGY 40: 1714-1724, 2012 ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion LI-JIE XIAO1,2*, PING LIN1*, FENG LIN1*, XIN LIU1, WEI QIN1, HAI-FENG ZOU1, LIANG GUO1, WEI LIU1, SHU-JUAN WANG1 and XIAO-GUANG YU1 1Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, 194 Xuefu Road, Harbin 150081, Heilongjiang; 2College of Life Science and Technology, Heilongjiang Bayi Agricultural University, 2 Xinyang Road, Daqing 163319, Heilongjiang, P.R. China Received September 8, 2011; Accepted November 18, 2011 DOI: 10.3892/ijo.2011.1320 Abstract. ADAM17, also known as tumor necrosis factor-α released and down-regulation of MMP-2, MMP-9. However, converting enzyme (TACE), is involved in proteolytic ectodo- these effects could be reversed by simultaneous addition of main shedding of cell surface molecules and cytokines. TGF-α. These data demonstrated that ADAM17 contributes to Although aberrant expression of ADAM17 has been shown androgen-independent prostate cancer cell invasion by shed- in various malignancies, the function of ADAM17 in prostate ding of EGFR ligand TGF-α, which subsequently activates the cancer has not been clarified. In the present study, we sought EGFR-MEK-ERK signaling pathway, leading finally to over- to elucidate whether ADAM17 contributes to prostate cancer expression of MMP-2 and MMP-9. This study suggests that the cell invasion, as well as the mechanism involved in the process. ADAM17 expression level may be a new predictive biomarker The expression pattern of ADAM17 was investigated in human of invasion and metastasis of prostate cancer, and ADAM17 prostate cancer cells. -
Mediates Neuronal Abeta42 Uptake and Lysosomal Trafficking Rodrigo A
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2010 Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking Rodrigo A. Fuentealba Washington University School of Medicine in St. Louis Qiang Liu Washington University School of Medicine in St. Louis Juan Zhang Washington University School of Medicine in St. Louis Takahisa Kanekiyo Washington University School of Medicine in St. Louis Xiaoyan Hu Washington University School of Medicine in St. Louis See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Part of the Medicine and Health Sciences Commons Recommended Citation Fuentealba, Rodrigo A.; Liu, Qiang; Zhang, Juan; Kanekiyo, Takahisa; Hu, Xiaoyan; Lee, Jin-Moo; LaDu, Mary Jo; and Bu, Guojun, ,"Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking." PLoS One.,. e11884. (2010). https://digitalcommons.wustl.edu/open_access_pubs/698 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Rodrigo A. Fuentealba, Qiang Liu, Juan Zhang, Takahisa Kanekiyo, Xiaoyan Hu, Jin-Moo Lee, Mary Jo LaDu, and Guojun Bu This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/698 Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Ab42 Uptake and Lysosomal Trafficking Rodrigo A. Fuentealba1,2., Qiang Liu1., Juan Zhang1, Takahisa Kanekiyo1, Xiaoyan Hu2, Jin-Moo Lee2, Mary Jo LaDu3, Guojun Bu1,4* 1 Department of Pediatrics, Washington University School of Medicine, St. -
Matrix Metalloproteinases in Angiogenesis: a Moving Target for Therapeutic Intervention
Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention William G. Stetler-Stevenson J Clin Invest. 1999;103(9):1237-1241. https://doi.org/10.1172/JCI6870. Perspective Angiogenesis is the process in which new vessels emerge from existing endothelial lined vessels. This is distinct from the process of vasculogenesis in that the endothelial cells arise by proliferation from existing vessels rather than differentiating from stem cells. Angiogenesis is an invasive process that requires proteolysis of the extracellular matrix and, proliferation and migration of endothelial cells, as well as synthesis of new matrix components. During embryonic development, both vasculogenesis and angiogenesis contribute to formation of the circulatory system. In the adult, with the single exception of the reproductive cycle in women, angiogenesis is initiated only in response to a pathologic condition, such as inflammation or hypoxia. The angiogenic response is critical for progression of wound healing and rheumatoid arthritis. Angiogenesis is also a prerequisite for tumor growth and metastasis formation. Therefore, understanding the cellular events involved in angiogenesis and the molecular regulation of these events has enormous clinical implications. This understanding is providing novel therapeutic targets for the treatment of a variety of diseases, including cancer. Whatever the pathologic condition, an initiating stimulus results in the formation of a migrating solid column of endothelial cells called the vascular sprout. The advancing front of this endothelial cell column presumably focuses proteolytic activity to create a defect in the extracellular matrix, through which the advancing and proliferating column of endothelial […] Find the latest version: https://jci.me/6870/pdf Matrix metalloproteinases in angiogenesis: Perspective a moving target for therapeutic intervention SERIES Topics in angiogenesis David A. -
Proteolytic Enzymes
Proteolytic Enzymes Proteolytic Stock Storage Concentration Reaction Enzyme Solution Temperature in Reaction Buffer Temperature Pretreatment 1 2 Pronase 20mg/mL in H2O –20°C 1mg/mL 0.01M Tris 37°C Self-digestion (pH 7.8) 0.01M EDTA 0.5% SDS 3 Proteinase K 20mg/mL in H2O –20°C 50µg/mL 0.01M Tris 37° to 56°C None required (pH 7.8) 0.005M EDTA 0.5% SDS 1 Pronase is a mixture of serine and acid proteases isolated from Streptomyces griseus. 2 Self-digestion eliminates contamination with DNase and RNase. Self-digested Pronase is prepared by dissolving powdered Pronase in 10mM Tris•Cl (pH 7.5), 10mM NaCl to a final concentration of 20mg/mL and incubating for 1 hour at 37°C. Store the self-digested Pronase in small aliquots at –20°C in tightly capped tubes. 3 Proteinase K is a highly active protease of the subtilisin type that is purified from the mould Tritirachium album Limber. The enzyme has two binding sites for Ca2+, which lie some distance from the active site and are not directly involved in the catalytic mechanism. However, when Ca2+ is removed from the enzyme, approxi- mately 80% of the catalytic activity is lost because of long-range structural changes (Bajorath et al. Nature 1989; 337:481-484). Because the residual activity is usually sufficient to degrade proteins that commonly contaminate preparations of nucleic acids, digestion with Proteinase K is usually carried out in the presence of EDTA (to inhibit the action of Mg2+-dependent nucleases). However, to digest highly resistant proteins such as keratin, it may be necessary to use a buffer con- taining 1mM Ca2+ and no EDTA. -
Gent Forms of Metalloproteinases in Hydra
Cell Research (2002); 12(3-4):163-176 http://www.cell-research.com REVIEW Structure, expression, and developmental function of early diver- gent forms of metalloproteinases in Hydra 1 2 3 4 MICHAEL P SARRAS JR , LI YAN , ALEXEY LEONTOVICH , JIN SONG ZHANG 1 Department of Anatomy and Cell Biology University of Kansas Medical Center Kansas City, Kansas 66160- 7400, USA 2 Centocor, Malvern, PA 19355, USA 3 Department of Experimental Pathology, Mayo Clinic, Rochester, MN 55904, USA 4 Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA ABSTRACT Metalloproteinases have a critical role in a broad spectrum of cellular processes ranging from the breakdown of extracellular matrix to the processing of signal transduction-related proteins. These hydro- lytic functions underlie a variety of mechanisms related to developmental processes as well as disease states. Structural analysis of metalloproteinases from both invertebrate and vertebrate species indicates that these enzymes are highly conserved and arose early during metazoan evolution. In this regard, studies from various laboratories have reported that a number of classes of metalloproteinases are found in hydra, a member of Cnidaria, the second oldest of existing animal phyla. These studies demonstrate that the hydra genome contains at least three classes of metalloproteinases to include members of the 1) astacin class, 2) matrix metalloproteinase class, and 3) neprilysin class. Functional studies indicate that these metalloproteinases play diverse and important roles in hydra morphogenesis and cell differentiation as well as specialized functions in adult polyps. This article will review the structure, expression, and function of these metalloproteinases in hydra. Key words: Hydra, metalloproteinases, development, astacin, matrix metalloproteinases, endothelin. -
Effects of Collagen-Derived Bioactive Peptides and Natural Antioxidant
www.nature.com/scientificreports OPEN Efects of collagen-derived bioactive peptides and natural antioxidant compounds on Received: 29 December 2017 Accepted: 19 June 2018 proliferation and matrix protein Published: xx xx xxxx synthesis by cultured normal human dermal fbroblasts Suzanne Edgar1, Blake Hopley1, Licia Genovese2, Sara Sibilla2, David Laight1 & Janis Shute1 Nutraceuticals containing collagen peptides, vitamins, minerals and antioxidants are innovative functional food supplements that have been clinically shown to have positive efects on skin hydration and elasticity in vivo. In this study, we investigated the interactions between collagen peptides (0.3–8 kDa) and other constituents present in liquid collagen-based nutraceuticals on normal primary dermal fbroblast function in a novel, physiologically relevant, cell culture model crowded with macromolecular dextran sulphate. Collagen peptides signifcantly increased fbroblast elastin synthesis, while signifcantly inhibiting release of MMP-1 and MMP-3 and elastin degradation. The positive efects of the collagen peptides on these responses and on fbroblast proliferation were enhanced in the presence of the antioxidant constituents of the products. These data provide a scientifc, cell-based, rationale for the positive efects of these collagen-based nutraceutical supplements on skin properties, suggesting that enhanced formation of stable dermal fbroblast-derived extracellular matrices may follow their oral consumption. Te biophysical properties of the skin are determined by the interactions between cells, cytokines and growth fac- tors within a network of extracellular matrix (ECM) proteins1. Te fbril-forming collagen type I is the predomi- nant collagen in the skin where it accounts for 90% of the total and plays a major role in structural organisation, integrity and strength2. -
Neprilysin Activity Assay Kit (MAK350)
Neprilysin Activity Assay Kit Catalog Number MAK350 Storage Temperature –20 C TECHNICAL BULLETIN Product Description Components Neprilysin, also known as neutral endopeptidase, The kit is sufficient for 100 fluorometric assays in enkephalinase, CD10, and common acute 96 well plates. lymphoblastic leukemia antigen, is a zinc-containing transmembrane metalloproteinase. It is able to NEP Assay Buffer 40 mL hydrolyze very important endogenous peptides, such as Catalog Number MAK350A natriuretic atrial factor, enkephalins, substance P, bradykinin and amyloid (A ) peptide. Thus, NEP is a Neprilysin (Lyophilized) 1 vial potentially therapeutic target in important pathological Catalog Number MAK350B conditions such as cardiovascular disease, prostate cancer, and Alzheimer’s disease. NEP has also been NEP Substrate (in DMSO) 15 L used as a biological marker in a type of childhood Catalog Number MAK350C leukemia. The detection of NEP in endometrial stromal cells has been proposed as a helpful tool in the Abz-Standard (1 mM) 100 L diagnosis of endometriosis. NEP is currently a focus of Catalog Number MAK350D major interest in cardiovascular and neurological research. Reagents and Equipment Required but Not Provided. The Neprilysin Activity Assay Kit utilizes the ability of an Pipetting devices and accessories active NEP to cleave a synthetic substrate, o-amino- (e.g., multichannel pipettor) benzoic acid (Abz)-based peptide, to release a free White opaque flatbottom 96 well plates fluorophore. The released Abz can be easily quantified Fluorescence multiwell plate reader, capable of using a fluorescence microplate reader. The substrate 37 C temperature setting is specific to NEP and can differentiate the NEP activity Refrigerated microcentrifuge capable of from trypsin and other structurally similar zinc RCF 12,000 g metalloproteinase in biological samples such as Protease Inhibitor Cocktail (contains 80 M angiotensin converting enzymes (ACE1 and ACE2) and Aprotinin) (Catalog Number P8340) endothelin converting enzymes (ECE1 and ECE2).