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https://www.readbyqxmd.com/read/28222221/elastase-2-an-angiotensin-ii-generating-enzyme-contributes-to-increased-ang-ii-in-resistance-arteries-of-mice-with-myocardial-infarction
#1
Christiane Becari, Marcondes A B Silva, Marina T Durand, Cibele M Prado, Eduardo B Oliveira, Mauricio S Ribeiro, Helio C Salgado, Maria Cristina O Salgado, Rita C Tostes
Angiotensin II (Ang II), whose generation largely depends on angiotensin-converting enzyme activity, mediates most of the renin-angiotensin-system effects. Elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, alternatively generates Ang II in rat arteries. Myocardial infarction (MI) leads to intense RAS activation, but mechanisms involved on Ang II-generation in resistance arteries are unknown. We hypothesized that ELA-2 contributes to vascular Ang II generation and to cardiac damage in mice submitted to MI...
February 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28222216/biochemical-characterization-of-an-extracellular-heat-stable-protease-from-serratia-liquefaciens-isolated-from-raw-milk
#2
François Baglinière, Rafael Locatelli Salgado, Cleonice Aparecida Salgado, Maria Cristina Dantas Vanetti
The protease Ser2 secreted by the psychrotrophic strain Serratia liquefaciens L53, a highly proteolytic strain isolated from Brazilian raw milk was purified and characterized. Using azocasein as substrate, Ser2 exhibited activity in a wide range of pH (5 to 10) and temperature (4 to 60 °C). The optimal activity was detected at pH 8.0 and at a temperature of 37 °C. This protease, still active at 4, 7, and 10 °C, was strongly inhibited by chelating agents and by dithiothreitol, a reducing agent. These results confirmed that Ser2 belongs to the peptidase family M10 and requires Ca(2+) , Zn(2+) , and disulfide bridges for stability...
February 21, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28222138/anti-trypanosomal-activity-of-non-peptidic-nitrile-based-cysteine-protease-inhibitors
#3
Antonio C B Burtoloso, Sérgio de Albuquerque, Mark Furber, Juliana C Gomes, Cristiana Gonçalez, Peter W Kenny, Andrei Leitão, Carlos A Montanari, José Carlos Quilles, Jean F R Ribeiro, Josmar R Rocha
The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Anti-trypanosomal activity against the CL Brener strain of T. cruzi was observed in the 0.1 μM to 1 μM range for three nitrile-based cysteine protease inhibitors based on two scaffolds known to be associated with cathepsin K inhibition. The two compounds showing the greatest potency against the trypanosome were characterized by EC50 values (0.12 μM and 0.25 μM) that were an order of magnitude lower than the corresponding Ki values measured against cruzain, a recombinant form of cruzipain, in an enzyme inhibition assay...
February 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28221789/raman-spectroscopy-reveals-selective-interactions-of-cytochrome-c-with-cardiolipin-that-correlate-with-membrane-permeability
#4
Jay P Kitt, David A Bryce, Shelley D Minteer, Joel M Harris
Permeabilization of the outer mitochondrial membrane is an integral step in apoptosis. The resulting release of pro-apoptotic signaling proteins leads to cell destruction through activation of the cysteine-aspartic protease (caspase) cascade. However, the mechanism of outer mitochondrial membrane (OMM) permeabilization remains unclear. It was recently shown that cytochrome c can induce pore formation in cardiolipin-containing phospholipid membranes leading to large dextran and protein permeability. In this work, the interaction of cytochrome c with cardiolpin-containing phospholipid vesicles, serving as models of the OMM, is investigated to probe cytochrome c-induced permeability...
February 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28220880/parenteral-administration-of-factor-xa-iia-inhibitors-limits-experimental-aortic-aneurysm-and-atherosclerosis
#5
Corey S Moran, Sai-Wang Seto, Smriti M Krishna, Surabhi Sharma, Roby J Jose, Erik Biros, Yutang Wang, Susan K Morton, Jonathan Golledge
Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE(-/-)) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE(-/-) mice...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220122/nf-%C3%AE%C2%BAb-links-tlr2-and-par1-to-soluble-immunomodulator-factor-secretion-in-human-platelets
#6
Pauline Damien, Fabrice Cognasse, Bernard Payrastre, Sherry L Spinelli, Neil Blumberg, Charles-Antoine Arthaud, Marie-Ange Eyraud, Richard P Phipps, Archibald McNicol, Bruno Pozzetto, Olivier Garraud, Hind Hamzeh-Cognasse
The primary toll-like receptor (TLR)-mediated immune cell response pathway common for all TLRs is MyD88-dependent activation of NF-κB, a seminal transcription factor for many chemokines and cytokines. Remarkably, anucleate platelets express the NF-κB machinery, whose role in platelets remains poorly understood. Here, we investigated the contribution of NF-κB in the release of cytokines and serotonin by human platelets, following selective stimulation of TLR2 and protease activated receptor 1 (PAR1), a classical and non-classical pattern-recognition receptor, respectively, able to participate to the innate immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219792/conjugative-type-iv-secretion-in-gram-positive-pathogens-trag-a-lytic-transglycosylase-and-endopeptidase-interacts-with-translocation-channel-protein-tram
#7
Verena Kohler, Ines Probst, Andreas Aufschnaiter, Sabrina Büttner, Lisa Schaden, Gerald Rechberger, Günther Koraimann, Elisabeth Grohmann, Walter Keller
Conjugative transfer plays a major role in the transmission of antibiotic resistance in bacteria. pIP501 is a Gram-positive conjugative model plasmid with the broadest transfer host-range known so far and is frequently found in Enterococcus faecalis and Enterococcus faecium clinical isolates. The pIP501 type IV secretion system is encoded by 15 transfer genes. In this work, we focus on the VirB1-like protein TraG, a modular peptidoglycan metabolizing enzyme, and the VirB8-homolog TraM, a potential member of the translocation channel...
February 17, 2017: Plasmid
https://www.readbyqxmd.com/read/28219684/development-of-magnetic-nanoparticle-based-calorimetric-assay-for-the-detection-of-bovine-mastitis-in-cow-milk
#8
Raja Chinnappan, Sana Al Attas, Gerrit Koop, Tine van Werven, Wendy E Kaman, Floris J Bikker, Mohammed Zourob
Mastitis in dairy cattle is an inflammatory reaction of the udder tissue. Mastitis increases plasmin levels, leading to an increased proteolysis of milk proteins such as casein, resulting in a significant decrease in milk quality and related dairy products. Due to its key-role in mastitis, we used plasmin proteolytic activity as a biomarker for the detection of mastitis in bovine mastitic milk. Inspired by earlier studies on protease activity using mastitic milk samples, we developed a simple colorimetric assay to distinguish mastitic milk from milk derived from healthy animals...
February 17, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28219449/ex-vivo-18-o-labeling-mass-spectrometry-identifies-a-peripheral-amyloid-%C3%AE-clearance-pathway
#9
Erik Portelius, Niklas Mattsson, Josef Pannee, Henrik Zetterberg, Magnus Gisslén, Hugo Vanderstichele, Eleni Gkanatsiou, Gabriela A N Crespi, Michael W Parker, Luke A Miles, Johan Gobom, Kaj Blennow
BACKGROUND: Proteolytic degradation of amyloid β (Aβ) peptides has been intensely studied due to the central role of Aβ in Alzheimer's disease (AD) pathogenesis. While several enzymes have been shown to degrade Aβ peptides, the main pathway of Aβ degradation in vivo is unknown. Cerebrospinal fluid (CSF) Aβ42 is reduced in AD, reflecting aggregation and deposition in the brain, but low CSF Aβ42 is, for unknown reasons, also found in some inflammatory brain disorders such as bacterial meningitis...
February 20, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28219118/bmcalpains-are-involved-in-autophagy-and-apoptosis-during-metamorphosis-and-after-starvation-in-bombyx-mori
#10
Hui-Yu Yi, Wan-Ying Yang, Wen-Mei Wu, Xing-Xia Li, Xiao-Juan Deng, Qing-Rong Li, Yang Cao, Yang-Jin Zhong, Ya-Dong Huang
Apoptosis and autophagy play crucial roles during Bombyx mori metamorphosis and in response to various adverse conditions, including starvation. Recently, calpain, one of the major intracellular proteases, has been reported to be involved in apoptosis and autophagy in mammals. BmATG5 and BmATG6 have been identified to mediate apoptosis following autophagy induced by 20-hydroxyecdysone and starvation in B. mori. However, B. mori calpains and their functions remain unclear. In this study, phylogenetic analysis of calpains from B...
November 7, 2016: Insect Science
https://www.readbyqxmd.com/read/28219045/modulating-the-selectivity-of-matriptase-2-inhibitors-with-unnatural-amino-acids
#11
Catherine St-Georges, Antoine Désilets, François Béliveau, Mariana Ghinet, Sébastien P Dion, Éloic Colombo, Pierre-Luc Boudreault, Rafael J Najmanovich, Richard Leduc, Éric Marsault
Matriptase-2, a type II transmembrane serine protease (TTSP), is expressed in the liver and regulates iron homeostasis via the cleavage of hemojuvelin. Matriptase-2 emerges as an attractive target for the treatment of conditions associated with iron overload, such as hemochromatosis or beta-thalassemia. Starting from the crystal structure of its closest homolog matriptase, we constructed a homology model of matriptase-2 in order to further optimize the selectivity of serine trap peptidomimetic inhibitors for matriptase-2 vs matriptase...
February 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28219017/interaction-between-fmdv-l-pro-and-transcription-factor-adnp-is-required-for-optimal-viral-replication
#12
Gisselle N Medina, Giselle M Knudsen, Alexander L Greninger, Anna Kloc, Fayna Díaz-San Segundo, Elizabeth Rieder, Marvin J Grubman, Joseph L DeRisi, Teresa de Los Santos
The foot-and-mouth disease virus (FMDV) leader protease (L(pro)) inhibits host translation and transcription affecting the expression of several factors involved in innate immunity. In this study, we have identified the host transcription factor ADNP (activity dependent neuroprotective protein) as an L(pro) interacting protein by mass spectrometry. We show that L(pro) can bind to ADNP in vitro and in cell culture. RNAi of ADNP negatively affected virus replication and higher levels of interferon (IFN) and IFN-stimulated gene expression were detected...
February 17, 2017: Virology
https://www.readbyqxmd.com/read/28218665/matrix-metalloproteinases-as-regulators-of-periodontal-inflammation
#13
REVIEW
Cavalla Franco, Hernández-Ríos Patricia, Sorsa Timo, Biguetti Claudia, Hernández Marcela
Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the 'protease web' is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218251/stim1-phosphorylation-at-y361-recruits-orai1-to-stim1-puncta-and-induces-ca-2-entry
#14
Pascal Yazbeck, Mohammad Tauseef, Kevin Kruse, Md-Ruhul Amin, Rayees Sheikh, Stefan Feske, Yulia Komarova, Dolly Mehta
Store-operated Ca(2+) entry (SOCE) mediates the increase in intracellular calcium (Ca(2+)) in endothelial cells (ECs) that regulates several EC functions including tissue-fluid homeostasis. Stromal-interaction molecule 1 (STIM1), upon sensing the depletion of (Ca(2+)) from the endoplasmic reticulum (ER) store, organizes as puncta that trigger store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+)-selective Orai1 channels. While the STIM1 and Orai1 binding interfaces have been mapped, signaling mechanisms activating STIM1 recruitment of Orai1 and STIM1-Orai1 interaction remains enigmatic...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217805/-induction-of-robust-senescence-associated-secretory-phenotype-in-mouse-nih-3t3-cells-by-mitomycin-c
#15
Wei-Xing Huang, Xiao-Xuan Guo, Zhong-Zhi Peng, Chun-Liang Weng, Chun-Yan Huang, Ben-Yan Shi, Jie Yang, Xiao-Xin Liao, Xiao-Yi Li, Hui-Ling Zheng, Xin-Guang Liu, Xue-Rong Sun
Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28217691/%C3%AE-1-antitrypsin-deficiency-a-misfolded-secretory-protein-variant-with-unique-effects-on-the-endoplasmic-reticulum
#16
David H Perlmutter
In the classical form of α1-antitrypsin deficiency (ATD) a point mutation leads to accumulation of a misfolded secretory glycoprotein in the endoplasmic reticulum (ER) of liver cells and so ATD has come to be considered a prototypical ER storage disease. It is associated with two major types of clinical disorders, chronic obstructive pulmonary disease (COPD) by loss-of-function mechanisms and hepatic cirrhosis and carcinogenesis by gain-of-function mechanisms. The lung disease predominantly results from proteolytic damage to the pulmonary connective tissue matrix because of reduced levels of protease inhibitor activity of α1-anitrypsin (AT) in the circulating blood and body fluids...
September 2016: Endoplasmic Reticulum Stress in Diseases
https://www.readbyqxmd.com/read/28217561/characterisation-of-the-thermostable-protease-aprx-in-strains-of-pseudomonas-fluorescens-and-impact-on-the-shelf-life-of-dairy-products-preliminary-results
#17
Nadia Andrea Andreani, Lisa Carraro, Luca Fasolato, Stefania Balzan, Rosaria Lucchini, Enrico Novelli, Barbara Cardazzo
Bacterial proteases are involved in food spoilage and shelf-life reduction. Among the bacterial proteases, a predominant role in spoilage of dairy products seems to be played by the thermostable metallo-protease AprX, which is produced by various strains of Pseudomonas fluorescens. Differences in AprX enzyme activity among different strains were highlighted, but the most proteolytic strains were not identified. In this study, the presence of the aprX gene was evaluated in 69 strains isolated from food matrices and 18 reference strains belonging to the P...
September 20, 2016: Italian Journal of Food Safety
https://www.readbyqxmd.com/read/28217559/a-novel-enterovirus-71-ev71-virulence-determinant-the-69th-residue-of-3c-protease-modulates-pathogenicity
#18
Bingqing Li, Yingying Yue, Yajie Zhang, Zenglin Yuan, Peng Li, Nannan Song, Wei Lin, Yan Liu, Lichuan Gu, Hong Meng
Human enterovirus type 71 (EV71), the major causative agent of hand-foot-and-mouth disease, has been known to cause fatal neurological complications. Unfortunately, the reason for neurological complications that have been seen in fatal cases of the disease and the relationship between EV71 virulence and viral genetic sequences remains largely undefined. The 3C protease (3C(pro)) of EV71 plays an irreplaceable role in segmenting the precursor polyprotein during viral replication, and intervening with host life activity during viral infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28217259/phase-3-trial-of-first-generation-protease-inhibitor-therapy-for-hepatitis-c-virus-human-immunodeficiency-virus-coinfection
#19
Kenneth E Sherman, Minhee Kang, Richard Sterling, Triin Umbleja, Kristen Marks, Jennifer J Kiser, Beverly Alston-Smith, Wayne Greaves, Adeel A Butt, The Actg Birth Study Team
AIM: To evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODS: A prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28216875/antidermatophytic-and-protease-inhibiting-activities-of-zerumbone-a-natural-sesquiterpene-from-the-rhizome-of-zingiber-zerumbet-l-roscoe-ex-j-e-smith
#20
Madhavankutty Jyothilakshmi, Mathew Jyothis, Gokulanathan Nair Hari Narayanan, Mukalel Sankunni Latha
CONTEXT: Due to increase in the number of patients with impaired immunity, incidence of dermatophytoses has increased considerably. Antidermatophytic agents with anti-inflammatory and protease-inhibiting activities will help in restricting inflammatory response associated with dermatophytoses. AIMS: The present study aims to evaluate antidermatophytic and protease-inhibiting activities of zerumbone. Cytotoxicity was tested using Chang liver cell line as a preliminary step in toxicity study...
January 2017: Pharmacognosy Magazine
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