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Cathepsin G

Man Kyu Shim, Hong Yeol Yoon, Ju Hee Ryu, Heebeom Koo, Sangmin Lee, Jae Hyung Park, Jong-Ho Kim, Seulki Lee, Martin G Pomper, Ick Chan Kwon, Kwangmeyung Kim
Recently, metabolic glycoengineering with bioorthogonal click reactions has focused on improving the tumor targeting efficiency of nanoparticles as delivery vehicles for anticancer drugs or imaging agents. It is the key technique for developing tumor-specific metabolic precursors that can generate unnatural glycans on the tumor-cell surface. A cathepsin B-specific cleavable substrate (KGRR) conjugated with triacetylated N-azidoacetyl-d-mannosamine (RR-S-Ac3 ManNAz) was developed to enable tumor cells to generate unnatural glycans that contain azide groups...
October 20, 2016: Angewandte Chemie
Khalil Bdeir, Kandace Gollomp, Marta Stasiak, Junjie Mei, Izabela Papiewska-Pajak, Guohua Zhao, G Scott Worthen, Douglas B Cines, Mortimer Poncz, M Anna Kowalska
RATIONALE: Platelets and neutrophils contribute to the development of acute lung injury (ALI). However, the mechanism by which platelets make this contribution is incompletely understood. We asked whether the two most abundant platelet chemokines, CXCL7, which induces neutrophil chemotaxis and activation, and CXCL4, which does neither, mediate ALI through complementary pathogenic pathways. OBJECTIVES: To examine the role of platelet-derived chemokines in the pathogenesis of ALI using Cxcl7-/- and Cxcl4-/- knockout mice and mice that express human CXCL7 or CXCL4...
October 18, 2016: American Journal of Respiratory Cell and Molecular Biology
G J Kelly, A Foltyn-Arfa Kia, F Hassan, S O'Grady, M P Morgan, B S Creaven, S McClean, J H Harmey, M Devocelle
Antimicrobial Peptides (AMPs) have unique anticancer properties, but their clinical application is currently limited by an inadequate margin of safety. A prodrug strategy associated with a combination therapy approach could address this limitation by increasing their therapeutic index and their efficacy. Accordingly, the first targeted anticancer polymeric prodrug candidates of AMPs, intended for combination therapy with another polymeric prodrug of an approved antineoplastic agent (doxorubicin), were synthesized as either a PEG-based dual-release prodrug or two individual pegylated prodrugs...
October 4, 2016: Organic & Biomolecular Chemistry
Jürgen Fritsch, Ricarda Fickers, Jan Klawitter, Vinzenz Särchen, Philipp Zingler, Dieter Adam, Ottmar Janssen, Eberhard Krause, Stefan Schütze
During apoptosis induction by TNF, the extrinsic and intrinsic apoptosis pathways converge at the lysosomal-mitochondrial interface. Earlier studies showed that the lysosomal aspartic protease Cathepsin D (CtsD) cleaves Bid to tBid, resulting in the amplification of the initial apoptotic cascade via mitochondrial outer membrane permeabilization (MOMP).The goal of this study was to identify further targets for CtsD that might be involved in activation upon death receptor ligation. Using a proteomics screen, we identified the heat shock protein 90 (HSP90) to be cleaved by CtsD after stimulation of U937 or other cell lines with TNF, FasL and TRAIL...
October 3, 2016: Oncotarget
Matthew Huisman, Jessica K White, Veronica G Lewalski, Izabela Podgorski, Claudia Turro, Jeremy J Kodanko
Photochemical control over irreversible inhibition was shown using Ru(ii)-caged inhibitors of cathepsin L. Levels of control were dependent on where the Ru(ii) complex was attached to the organic inhibitor, reaching >10 : 1 with optimal placement. A new strategy for photoreleasing Ru(ii) fragments from inhibitor-enzyme conjugates is also reported.
October 18, 2016: Chemical Communications: Chem Comm
Amanda J Stock, Anne Kasus-Jacobi, Jonathan D Wren, Virginie H Sjoelund, Glenn D Prestwich, H Anne Pereira
We previously showed an elevated expression of the neutrophil protein, cationic antimicrobial protein of 37kDa (CAP37), in brains of patients with Alzheimer's disease (AD), suggesting that CAP37 could be involved in AD pathogenesis. The first step in determining how CAP37 might contribute to AD pathogenesis was to identify the receptor through which it induces cell responses. To identify a putative receptor, we performed GAMMA analysis to determine genes that positively correlated with CAP37 in terms of expression...
2016: PloS One
H P T Ammon
: Boswellic acids, which are pentacyclic triterpenes belong to the active pharmacological compounds of the oleogum resin of different Boswellia species. In the resin, more than 12 different boswellic acids have been identified but only KBA and AKBA received significant pharmacological interest. Biological Activity: In an extract of the resin of Boswellia species multiple factors are responsible for the final outcome of a therapeutic effect, be it synergistic or antagonistic. Moreover, the anti-inflammatory actions of BAs are caused by different mechanisms of action...
2016: Advances in Experimental Medicine and Biology
Adriane Penczek, Marcin Sienczyk, Christian Rainer Wirtz, Timo Burster
Natural killer (NK) cells are critical in diverse defense mechanisms, including elimination of viral infected cells and destruction of tumor cells. NK cells are characterized by the ability to initiate apoptosis in target cells when their cell surface major histocompatibility complex class I (MHC I) repertoire is missing. On the other hand, NK cells are not activated when MHC I or non-classical MHC molecules are found on the respective cells. It was demonstrated that cathepsin G (CatG) binds to the cell surface of NK cells; however, the distribution of this protease on the cell surface of NK cell subsets has not been identified...
September 24, 2016: Immunology Letters
Almudena Ortega Gomez, Melanie Salvermoser, Jan Rossaint, Robert Pick, Janine Brauner, Patricia Lemnitzer, Jessica Tilgner, Renske de Jong, Remco T A Megens, Janina Jamasbi, Yvonne Döring, Christine T Pham, Christoph Scheiermann, Wolfgang Siess, Maik Drechsler, Christian Weber, Jochen Grommes, Alexander Zarbock, Barbara Walzog, Oliver Soehnlein
BACKGROUND: -Therapeutic targeting of arterial leukocyte recruitment in the context of atherosclerosis has been disappointing in clinical studies. Reasons for such failures include the lack of knowledge of arterial-specific recruitment patterns. Here we establish the importance of the Cathepsin G (CatG) in the context of arterial myeloid cell recruitment. METHODS: -Intravital microscopy of the carotid artery, the jugular vein and cremasteric arterioles and venules in Apoe(-/-) and CatG-deficient mice Apoe(-/-)Ctsg(-/-)) mice was employed to study site-specific myeloid cell behavior after high fat diet (HFD) feeding or TNF stimulation...
September 22, 2016: Circulation
Ivana Musilova, Ctirad Andrys, Marcela Drahosova, Ondrej Soucek, Lenka Pliskova, Martin Stepan, Tomas Bestvina, Jan Maly, Bo Jacobsson, Marian Kacerovsky
OBJECTIVE: The aim of this study was to evaluate the amniotic fluid cathepsin-G concentrations in women with preterm prelabor rupture of membranes (PPROM) based on the presence of the microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI). METHODS: A total of 154 women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid cathepsin-G concentrations were assessed by ELISA...
October 9, 2016: Journal of Maternal-fetal & Neonatal Medicine
Gabriel Nasri Marzuca-Nassr, Kaio Fernando Vitzel, Luís Gustavo De Sousa, Gilson M Murata, Amanda Rabello Crisma, Carlos Flores Rodrigues Junior, Phablo Abreu, Rosângela Pavan Torres, Jorge Mancini-Filho, Sandro M Hirabara, Philip Newsholme, Rui Curi
The effects of either eicosapentaenoic (EPA)- or docosahexaenoic (DHA)-rich fish oils on hindlimb suspension (HS)-induced muscle disuse atrophy were compared. Daily oral supplementations (0.3 mL/100 g b.w.) with mineral oil (MO) or high EPA or high DHA fish oils were performed in adult rats. After 2 weeks, the animals were subjected to HS for further 2 weeks. The treatments were maintained alongside HS At the end of 4 weeks, we evaluated: body weight gain, muscle mass and fat depots, composition of fatty acids, cross-sectional areas (CSA) of the soleus muscle and soleus muscle fibers, activities of cathepsin L and 26S proteasome, and content of carbonylated proteins in the soleus muscle...
September 2016: Physiological Reports
Xue Li, Zhou Wu, Junjun Ni, Yicong Liu, Jie Meng, Weixian Yu, Hiroshi Nakanishi, Yanmin Zhou
Fibroblasts are essential for tissue repair due to producing collagens, and lysosomal proteinase cathepsin B (CatB) is involved in promoting chronic inflammation. We herein report that CatB regulates the expression of collagens III and IV by fibroblasts in response to a TLR2 agonist, lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). In cultured human BJ fibroblasts, mRNA expression of CatB was significantly increased, while that of collagens III and IV was significantly decreased at 24 h after challenge with P...
2016: Oxidative Medicine and Cellular Longevity
Bruna Benso, Marcelo Franchin, Adna Prado Massarioli, Jonas Augusto Rizzato Paschoal, Severino Matias Alencar, Gilson Cesar Nobre Franco, Pedro Luiz Rosalen
Given their medical importance, natural products represent a tremendous source of drug discovery. The aim of this study was to investigate Malva sylvestris L. extract and fractions and their pharmacological activities followed by chemical identification. The aqueous fraction (AF) was identified as the bioactive fraction in the in vitro and in vivo assays. The AF controlled the neutrophil migration to the peritoneal cavity by 66%, inhibited the antiedematogenic activity by 58.8%, and controlled IL-1β cytokine expression by 54%...
2016: PloS One
Dave Koole, Joost A van Herwaarden, Casper G Schalkwijk, Floris P J G Lafeber, Aryan Vink, Mirjam B Smeets, Gerard Pasterkamp, Frans L Moll
BACKGROUND: Diabetes is a risk factor for atherosclerotic disease but negatively associated with the development and progression of abdominal aortic aneurysm (AAA). Advanced glycation end products (AGEs) are increased in diabetes and renders the vascular matrix more resistant to proteolysis. We assessed the concentration of AGEs in AAA biopsies obtained from diabetic and nondiabetic patients and hypothesized that (nonenzymatic) glycation of AAA tissue protects against proteolytic breakdown of collagen...
September 10, 2016: Journal of Vascular Surgery
G A Fedorova, E S Korneva, A S Belikova, M A Grachev
Silicateins are proteins found within spicules of siliceous sponges. They are analogs of proteinases cathepsins; they catalyze the transformation of silicic acid esters into biogenic silica (SiO2 ·nH2 O), and are believed to take part in the processes of silicification in marine and freshwater sponges. Earlier studies by Kalyuzhnaya et al. revealed that the Baikal Sponge Lubomirskia baicalensis Pallas, 1773 (L. baicalensis) contains a gene 1988 bp long, which hosts four sequences that encode four mRNAs giving rise to silicateins α1, α2, α3 and α4 (SILα1, SILα2, SILα3, SILα4) whose predicted amino acid sequences are similar to those of the predicted sequences of marine sponge silicateins...
September 12, 2016: Protein Science: a Publication of the Protein Society
Alexandre Valayer, Deborah Brea, Laurie Lajoie, Leslie Avezard, Lucie Combes-Soia, Valerie Labas, Brice Korkmaz, Gilles Thibault, Thomas Baranek, Mustapha Si-Tahar
Polymorphonuclear neutrophils (PMNs) can contribute to the regulation of the host immune response by crosstalk with innate and adaptive leukocytes, including NK cells. Mechanisms by which this immunoregulation process occurs remain incompletely understood. Here, we focused on the effect of human neutrophil-derived serine proteases on NKp46, a crucial activating receptor expressed on NK cells. We used flow cytometry, Western blotting, and mass spectrometry (MS) analysis to reveal that cathepsin G [CG; and not elastase or proteinase 3 (PR3)] induces a time- and concentration-dependent, down-regulatory effect on NKp46 expression through a restricted proteolytic mechanism...
September 1, 2016: Journal of Leukocyte Biology
Xiukun Cui, Huiyuan Liu, Jing Li, Kangwen Guo, Wenxiu Han, Yi Dong, Simin Wan, Xuance Wang, Panpan Jia, Shulian Li, Yuanfang Ma, Jun Zhang, Hongmei Mu, Yanzhong Hu
Activation of Heat shock factor 4-mediated heat shock response is closely associated with postnatal lens development. HSF4 controls the expression of small heat shock proteins (e.g. HSP25 and CRYAB) in lens epithelial cells. However, their roles in modulating lens epithelium homeostasis remain unclear. In this paper, we find that HSF4 is developmentally expressed in mouse lens epithelium and fiber tissue. HSF4 and alpha B-crystallin can selectively protect lens epithelial cells from cisplatin and H2O2 induced apoptosis by stabilizing mitochondrial membrane potential (ΔYm) and reducing ROS production...
October 2016: International Journal of Biochemistry & Cell Biology
Marjolein Garsen, Angelique L W M M Rops, Henry Dijkman, Brigith Willemsen, Toin H van Kuppevelt, Frans G Russel, Ton J Rabelink, Jo H M Berden, Thomas Reinheckel, Johan van der Vlag
Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of proteins that are important for normal podocyte architecture, such as the CD2-associated protein, synaptopodin, and dynamin. Cathepsin L also activates heparanase, a heparan sulfate endoglycosidase previously shown to be crucial for the development of diabetic nephropathy...
November 2016: Kidney International
G Alatrash, H R Garber, M Zhang, P Sukhumalchandra, Y Qiu, H Jakher, A A Perakis, L Becker, S Y Yoo, K C Dwyer, K Coombes, A H Talukder, L S St John, V Senyukov, D A Lee, A Sergeeva, H He, Q Ma, P M Armistead, J Roszik, E A Mittendorf, J J Molldrem, D Hawke, G Lizee, S M Kornblau
Leukemia accepted article preview online, 30 August 2016. doi:10.1038/leu.2016.249.
August 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Hang Yang, Mona Helena Biermann, Jan Markus Brauner, Yi Liu, Yi Zhao, Martin Herrmann
Recent data suggest that NETosis plays a crucial role in the innate immune response and disturbs the homeostasis of the immune system. NETosis is a form of neutrophil-specific cell death characterized by the release of large web-like structures referred to as neutrophil extracellular traps (NETs). NETs are composed of DNA strands associated with histones and decorated with about 20 different proteins, including neutrophil elastase, myeloperoxidase, cathepsin G, proteinase 3, high mobility group protein B1, and LL37...
2016: Frontiers in Immunology
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