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https://www.readbyqxmd.com/read/29306874/a-structurally-dynamic-n-terminal-region-drives-function-of-the-staphylococcal-peroxidase-inhibitor-spin
#1
Nienke W M de Jong, Nicoleta T Ploscariu, Kasra X Ramyar, Brandon L Garcia, Alvaro I Herrera, Om Prakash, Benjamin B Katz, Kevin G Leidal, William Nauseef, Kok van Kessel, Jos van Strijp, Brian V Geisbrecht
The heme-containing enzyme myeloperoxidase (MPO) is critical for optimal antimicrobial activity of human neutrophils. We recently discovered that the bacterium Staphylococcus aureus expresses a novel immune evasion protein, called SPIN, that binds tightly to MPO, inhibits MPO activity, and contributes to bacterial survival following phagocytosis. A co-crystal structure of SPIN bound to MPO suggested that SPIN blocks substrate access to the catalytic heme by inserting an N-terminal β-hairpin into the MPO active site channel...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29305429/back-to-the-future-new-target-validated-rab-antibodies-for-evaluating-lrrk2-signalling-in-cell-biology-and-parkinson-s-disease
#2
Patrick A Eyers
The addition of phosphate groups to substrates allows protein kinases to regulate a myriad of biological processes, and contextual analysis of protein-bound phosphate is important for understanding how kinases contribute to physiology and disease. Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase linked to familial and sporadic cases of Parkinson's disease (PD). Recent work established that multiple Rab GTPases are physiological substrates of LRRK2, with Rab10 in particular emerging as a human substrate whose site-specific phosphorylation mirrors hyperactive LRRK2 lesions associated with PD...
January 5, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29296907/tlr2-agonism-reverses-chemotherapy-induced-neutropenia-in-macaca-fascicularis
#3
Nicholas J Laping, Michael P DeMartino, Joshua E Cottom, Jeffrey M Axten, John G Emery, Jeffrey H Guss, Miriam Burman, James J Foley, Mui Cheung, Allen Oliff, Sanjay Kumar
Neutropenia is a common consequence of radiation and chemotherapy in cancer patients. The resulting immunocompromised patients become highly susceptible to potentially life-threatening infections. Granulocyte colony-stimulating factor (G-CSF) is known to stimulate neutrophil production and is widely used as a treatment of chemotherapy-induced neutropenia. A small-molecule G-CSF secretagogue without a requirement for refrigerated supply chain would offer a more convenient and cost-effective treatment of chemotherapy-induced neutropenia...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29258826/a-multi-substrate-assay-for-finding-physiologically-effective-inhibitors-of-myeloperoxidase
#4
Louisa V Forbes, Anthony J Kettle
Myeloperoxidase, an abundant neutrophil enzyme, promotes oxidative damage during inflammation by generating hypohalous acids and free radicals. Currently, there are no selective drugs to inhibit its adverse activity. This short-coming is partly due to the lack of screening assays that mimic the complex enzymatic activities of myeloperoxidase in vivo. We have developed an assay for myeloperoxidase activity that includes its major physiological substrates - chloride, thiocyanate, tyrosine, and urate. The multi-substrate assay monitors bleaching of 5-thio-2-nitrobenzoic acid and measures total oxidant production when hydrogen peroxide activates the enzyme...
December 16, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29187682/bacterial-glycerol-oxidation-coupled-to-sulfate-reduction-at-neutral-and-acidic-ph
#5
Sidnei C Santos, Martin G Liebensteiner, Antonie H van Gelder, Mauricio R Dimitrov, Paulo F Almeida, Cristina M Quintella, Alfons J M Stams, Irene Sánchez-Andrea
Glycerol is a main co-product of biodiesel production. Crude glycerol may serve as a cheap and attractive substrate in biotechnological applications, e.g. for the production of valuable chemicals or as an electron donor for reduction processes. In this work, sulfate reduction with glycerol was studied at neutral and acidic pH using bioreactor sludge samples and Tinto River sediments as a source of inoculum, respectively. Communities of sulfate-reducing bacteria (SRB) and fermentative bacteria were co-enriched at both pH values...
November 29, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/29177697/neuroprotective-and-anti-inflammatory-effects-of-a-dodecamer-peptide-harboring-ninjurin-1-cell-adhesion-motif-in-the-postischemic-brain
#6
Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Lidan Luo, Seung-Woo Kim, Ja-Kyeong Lee
It has been reported that the innate immune response plays important roles in brain ischemia and that the infiltration of blood-derived immune cells is a key initiator of this response. Nerve injury-induced protein 1 (Ninjurin 1, Ninj1) is a cell adhesion molecule responsible for cell-to-cell interactions between immune cells and endothelial cells. In the present study, we investigated the proinflammatory and neuroprotective effects of Ninj1 and a dodecamer peptide harboring Ninj1 N-terminal adhesion motif (N-NAM, Pro26~Asn37) in a rat middle cerebral artery occlusion (MCAO) model of stroke...
November 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29175302/matrix-metalloproteinase-and-heparin-stimulated-serine-proteinase-activities-in-post-prostate-massage-urine-of-men-with-prostate-cancer
#7
David Muñoz, Maria K Serrano, Maria E Hernandez, Ross Haller, Tamara Swanson, Joel W Slaton, Akhouri A Sinha, Michael J Wilson
Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography...
December 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29158506/the-ikk-nf-%C3%AE%C2%BAb-signaling%C3%A2-pathway-requires-morgana-to-drive-breast-cancer-metastasis
#8
Federica Fusella, Laura Seclì, Elena Busso, Anna Krepelova, Enrico Moiso, Stefania Rocca, Laura Conti, Laura Annaratone, Cristina Rubinetto, Maurizia Mello-Grand, Vijay Singh, Giovanna Chiorino, Lorenzo Silengo, Fiorella Altruda, Emilia Turco, Alessandro Morotti, Salvatore Oliviero, Isabella Castellano, Federica Cavallo, Paolo Provero, Guido Tarone, Mara Brancaccio
NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29031206/inhibitory-effect-of-triperygium-wilfordii-polyglucoside-on-dipeptidyl-peptidase-i-in-vivo-and-in-vitro
#9
Jingjing Wang, Yi Chu, Xiaoying Zhou
BACKGROUD: Dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease is derived from granule immune cells including mast cell, neutrophils, and toxicity T cells. DPPI can activate serine proteases by removal of dipeptides from N-termini of the pro-proteases, resulting in granule immune cells activation which involved in physiological or pathological responses. Triperygium Wilfordii Polyglucoside (TWP) is one of the traditional Chinese medicines, and commonly used in rheumatoid arthritis (RA) treatment...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29022841/designing-cellulosic-and-nanocellulosic-sensors-for-interface-with-a-protease-sequestrant-wound-dressing-prototype-implications-of-material-selection-for-dressing-and-protease-sensor-design
#10
Krystal R Fontenot, J Vincent Edwards, David Haldane, Nicole Pircher, Falk Liebner, Brian D Condon, Huzaifah Qureshi, Dorne Yager
Interfacing nanocellulosic-based biosensors with chronic wound dressings for protease point of care diagnostics combines functional material properties of high specific surface area, appropriate surface charge, and hydrophilicity with biocompatibility to the wound environment. Combining a protease sensor with a dressing is consistent with the concept of an intelligent dressing, which has been a goal of wound-dressing design for more than a quarter century. We present here biosensors with a nanocellulosic transducer surface (nanocrystals, nanocellulose composites, and nanocellulosic aerogels) immobilized with a fluorescent elastase tripeptide or tetrapeptide biomolecule, which has selectivity and affinity for human neutrophil elastase present in chronic wound fluid...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28978524/ring-finger-protein-113a-regulates-c-x-c-chemokine-receptor-type-4-stability-and-signaling
#11
Travis Lear, Sarah R Dunn, Alison C McKelvey, Aazrin Mir, John Evankovich, Bill B Chen, Yuan Liu
As an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1, also called CXCL12), CXCR4 plays a vital role in chemotactically attracting lymphocytes during inflammation. CXCR4 also regulates HIV infection due to its role as one of the chemokine co-receptors for HIV entry into CD4+ T cells. Chemokine receptors and their signaling pathways have been shown to be regulated by the process of ubiquitination, a post-translational modification, guided by ubiquitin E3 ligases, which covalently links ubiquitin chains to lysine residues within target substrates...
October 4, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28968119/potential-anti-inflammatory-effects-of-the-fruits-of-paulownia-tomentosa
#12
Hyung Won Ryu, Yhun Jung Park, Su Ui Lee, Seoghyun Lee, Heung Joo Yuk, Kyeong-Hwa Seo, Yeah-Un Kim, Bang Yeon Hwang, Sei-Ryang Oh
As part of an ongoing search for new natural products from medicinal plants to treat respiratory disease, six new compounds, a dihydroflavonol (1) and five C-geranylated flavanones (3, 6, 8, 13, and 14), and 13 known compounds were isolated from mature fruits of Paulownia tomentosa. The structures of the new compounds were determined via interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, ECD, and MS). In biological activity assays with human alveolar basal epithelial cells, the expression of TNF-α-induced proinflammatory cytokines (IL-8 and IL-6) was reduced significantly by the EtOAc fraction of a P...
October 27, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28935640/attenuation-of-pulmonary-ace2-activity-impairs-inactivation-of-des-arg9-bradykinin-bkb1r-axis-and-facilitates-lps-induced-neutrophil-infiltration
#13
Chhinder P Sodhi, Christine Wohlford-Lenane, Yukihiro Yamaguchi, Thomas Prindle, William B Fulton, Sanxia Wang, Paul B McCray, Mark C Chappell, David J Hackam, Hongpeng Jia
Angiotensin converting enzyme 2 (ACE2) is a terminal carboxypeptidase with important functions in the renin angiotensin system and plays a critical role in inflammatory lung diseases. ACE2 cleaves single terminal residues from several bioactive peptides such as angiotensin II. However, few of its substrates in the respiratory tract have been identified and the mechanism underlying the role of ACE2 in inflammatory lung disease has not been fully characterized. In an effort to identify biological targets of ACE2 in the lung, we tested its effects on des-arg9 bradykinin (DABK) in airway epithelial cells based upon a hypothesis that DABK is a biological substrate of ACE2 in the lung and ACE2 plays an important role in the pathogenesis of acute lung inflammation partly through modulating DABK/BKB1R axis signaling...
September 21, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28905697/luteolibacter-gellanilyticus-sp-nov-a-gellan-gum-degrading-bacterium-of-the-phylum-verrucomicrobia-isolated-from-miniaturized-diffusion-chambers
#14
Javier Pascual, Marina García-López, Ignacio González, Olga Genilloud
A novel chemo-organoheterotrophic bacterium, strain CB-286403(T), was isolated from a Mediterranean forest soil, collected at Sierra de Tejeda, Almijara and Alhama Natural Park, Spain, by using the Diffusion Sandwich System, a device with 384 miniature diffusion chambers. The 16S rRNA gene sequence analyses identified the isolate as a member of the genus Luteolibacter where the type strains Luteolibacterpohnpeiensis A4T-83(T) (GenBank acc. no. AB331895), Luteolibacteryonseiensis EBTL01(T) (JQ319003), Luteolibacterluojiensis DR4-30(T) (JN630810) and Luteolibacteralgae A5J-41-2(T) (AB331893) were the closest relatives with similarities of 97...
October 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28881492/a-novel-elane-mutation-associated-with-inflammatory-arthritis-defective-netosis-and-recurrent-parvovirus-infection
#15
Uma Thanarajasingam, Mark A Jensen, Jessica M Dorschner, Theresa Wampler Muskardin, Yogita Ghodke-Puranik, Monica Purmalek, Elias Eliopoulos, Maria I Zervou, George N Goulielmos, Matthew Howard, Mariana J Kaplan, Timothy B Niewold
OBJECTIVE: We describe a 38-year-old woman who presented with a history of inflammatory arthritis, rash, and daily fevers. She was noted to have chronic parvovirus infection with persistently detectable viral titers and a novel mutation in the ELANE gene. ELANE encodes neutrophil elastase, a neutrophil serine protease with important antimicrobial effects, and is found as part of neutrophil extracellular trap (NET) complexes. Pathogenic ELANE mutations have been identified in forms of hereditary neutropenia...
September 7, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28843171/the-f0f1-atp-synthase-regulates-human-neutrophil-migration-through-cytoplasmic-proton-extrusion-coupled-with-atp-generation
#16
Jun Gao, Tian Zhang, Zhanfang Kang, Weijen Ting, Lingqing Xu, Dazhong Yin
Cytoplasmic alkalinization and extracellular adenosine triphosphate (ATP) signals are required for migration of chemokineactivated neutrophils, but the precise functions remain unclear. In this work, the effect of the plasma membrane-expressed F0F1-ATP synthase (FATPase) on human neutrophils was examined. We found F-ATPase to be involved in cytoplasm proton extrusion and extracellular ATP generation. Oligomycin A, an F-ATPase inhibitor that blocks proton transfer, inhibited cytoplasmic alkalinization, extracellular ATP generation, adhesion and chemotaxis in N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophils; however, adenosine diphosphate (ADP), a substrate and activator of F-ATPase, had the opposite effect...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28821572/rolling-neutrophils-form-tethers-and-slings-under-physiologic-conditions-in-vivo
#17
Alex Marki, Konrad Buscher, Zbigniew Mikulski, Axel Pries, Klaus Ley
Human and mouse neutrophils are known to form tethers when rolling on selectins in vitro. Tethers are ∼0.2 μm thin, ∼5-10 μm-long structures behind rolling cells that can swing around to form slings that serve as self-adhesive substrates. Here, we developed a mouse intravital imaging method, where the neutrophil surface is labeled by injecting fluorescently labeled mAb to Ly-6G. Venules in the cremaster muscle of live mice were imaged at a high frame rate using a confocal microscope equipped with a fast resonant scanner...
August 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28808028/immune-evasion-by-a-staphylococcal-inhibitor-of-myeloperoxidase
#18
Nienke W M de Jong, Kasra X Ramyar, Fermin E Guerra, Reindert Nijland, Cindy Fevre, Jovanka M Voyich, Alex J McCarthy, Brandon L Garcia, Kok P M van Kessel, Jos A G van Strijp, Brian V Geisbrecht, Pieter-Jan A Haas
Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein "staphylococcal peroxidase inhibitor" (SPIN)...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28806402/multi-functional-mechanisms-of-immune-evasion-by-the-streptococcal-complement-inhibitor-c5a-peptidase
#19
Nicola N Lynskey, Mark Reglinski, Damien Calay, Matthew K Siggins, Justin C Mason, Marina Botto, Shiranee Sriskandan
The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28760594/s-oxiracetam-protect-against-ischemic-stroke-via-alleviating-blood-brain-barrier-dysfunction-in-rats
#20
Liangliang Huang, Erxin Shang, Wenxiang Fan, Xiang Li, Binbin Li, Shucheng He, Yuxin Fu, Yizhi Zhang, Yunman Li, Weirong Fang
The blood brain barrier (BBB) maintains the basic stability of the brain tissue under physiological conditions, while destroys and exaggerates brain edema and inflammatory response after ischemic stroke. In this study, we researched S-oxiracetam (S-ORC), a nootropic drug, alleviates BBB dysfunction and protects against ischemic stroke in rats. Middle cerebral artery occlusion(MCAO)/reperfusion in rats is applied to mimic ischemic stroke. One hour after reperfusion, rats are administered intravenously with different dose (0...
July 29, 2017: European Journal of Pharmaceutical Sciences
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