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Cathepsin G

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https://www.readbyqxmd.com/read/28424202/global-protease-activity-profiling-provides-differential-diagnosis-of-pancreatic-cysts
#1
Sam L Ivry, Jeremy M Sharib, Dana A Dominguez, Nilotpal Roy, Stacy E Hatcher, Michele Yip-Schneider, C Max Schmidt, Randall E Brand, Walter G Park, Matthias Hebrok, Grace Kim, Anthony J O'Donoghue, Kimberly S Kirkwood, Charles S Craik
Pancreatic cysts are estimated to be present 2-3% of the adult population. Unfortunately, current diagnostics do not accurately distinguish benign cysts from those that can progress into invasive cancer. Missregulated pericellular proteolysis is a hallmark of malignancy, and therefore, we used a global approach to discover protease activities that differentiate benign nonmucinous cysts from premalignant mucinous cysts.<br /><br />Experimental Design: We employed an unbiased and global protease profiling approach to discover protease activities in 23 cyst fluid samples...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28403897/trypanosoma-vivax-is-the-second-leading-cause-of-camel-trypanosomosis-in-sudan-after-trypanosoma-evansi
#2
Ehab Mossaad, Bashir Salim, Keisuke Suganuma, Peter Musinguzi, Mohammed A Hassan, E A Elamin, G E Mohammed, Amel O Bakhiet, Xuenan Xuan, Rawan A Satti, Noboru Inoue
BACKGROUND: This study was conducted in response to recurring reports from eastern Sudan of camel trypanosomosis that can no longer be treated by currently available trypanocidal drugs. One hundred and eighty-nine blood samples were obtained from camels in different herds and local markets in the western part of Sudan, and a cross-sectional study was carried out between December 2015 and February 2016 to identify the causative agents and possible circulating genotypes. RESULTS: The prevalence of trypanosomes detected using the conventional parasitological techniques of Giemsa-stained blood smears, wet blood smears and the microhematocrit centrifugation technique (MHCT) was 7% (13/189), 11% (21/189) and 19% (36/189), respectively...
April 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28403145/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection
#3
Elizabeth A Nelson, Julie Dyall, Thomas Hoenen, Alyson B Barnes, Huanying Zhou, Janie Y Liang, Julia Michelotti, William H Dewey, Lisa Evans DeWald, Richard S Bennett, Patrick J Morris, Rajarshi Guha, Carleen Klumpp-Thomas, Crystal McKnight, Yu-Chi Chen, Xin Xu, Amy Wang, Emma Hughes, Scott Martin, Craig Thomas, Peter B Jahrling, Lisa E Hensley, Gene G Olinger, Judith M White
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM)...
April 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28374518/neutrophil-extracellular-traps-can-serve-as-platforms-for-processing-and-activation-of-il-1-family-cytokines
#4
Danielle M Clancy, Conor M Henry, Graeme P Sullivan, Seamus J Martin
Activated neutrophils can undergo a mode of regulated cell death, called NETosis, that results in the extrusion of chromatin into the extracellular space, thereby acting as extracellular traps for microorganisms. Neutrophil-derived extracellular traps (NETs) are comprised of DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such as elastase and cathepsin G. NET-associated factors are thought to enhance the anti-microbial properties of these structures and localisation of anti-microbial molecules on NETs may serve to increase their local concentration...
April 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28364042/kinetic-based-trapping-by-intervening-sequence-variants-of-the-active-sites-of-protein-disulfide-isomerase-identifies-platelet-protein-substrates
#5
Jack D Stopa, Katherine M Baker, Steven P Grover, Robert Flaumenhaft, Bruce Furie
Thiol isomerases such as protein disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging since PDI catalyzes conformational changes that cannot be easily monitored (e.g., compared with proteolytic cleavage or amino acid phosphorylation), PDI has multiple substrates, and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28363962/mechanisms-for-pseudoalteromonas-piscicida-induced-killing-of-vibrios-and-other-bacterial-pathogens
#6
Gary P Richards, Michael A Watson, David S Needleman, Joseph Uknalis, E Fidelma Boyd, Johnna P Fay
Pseudoalteromonas piscicida are Gram-negative Gammaproteobacteria found in the marine environment. Three strains of pigmented P. piscicida were isolated from seawater and partially characterized by inhibition studies, electron microscopy, and proteolytic enzyme production. Growth inhibition and death occurred around colonies of P. piscicida on lawns of the naturally-occurring marine pathogens Vibrio vulnificus, V. parahaemolyticus, V. cholerae, Photobacterium damselae and Shewanella algae Inhibition also occurred on lawns of Staphylococcus aureus, but not on Escherichia coli O157:H7 or Salmonella enterica serovar Typhimurium...
March 31, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28348600/delivery-of-bone-marrow-derived-mesenchymal-stem-cells-improves-tear-production-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#7
Hema S Aluri, Mahta Samizadeh, Maria C Edman, Dillon R Hawley, Helene L Armaos, Srikanth R Janga, Zhen Meng, Victor G Sendra, Pedram Hamrah, Claire L Kublin, Sarah F Hamm-Alvarez, Driss Zoukhri
The purpose of the present study was to test the potential of mouse bone marrow-derived mesenchymal stem cells (BD-MSCs) in improving tear production in a mouse model of Sjögren's syndrome dry eye and to investigate the underlying mechanisms involved. NOD mice (n = 20) were randomized to receive i.p. injection of sterile phosphate buffered saline (PBS, control) or murine BD-MSCs (1 × 10(6) cells). Tears production was measured at baseline and once a week after treatment using phenol red impregnated threads...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28336537/muscle-specific-and-age-related-changes-in-protein-synthesis-and-protein-degradation-in-response-to-hindlimb-unloading-in-rats
#8
Leslie M Baehr, Daniel W D West, Andrea G Marshall, George R Marcotte, Keith Baar, Sue C Bodine
Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7 or 14 days...
March 23, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28326926/potential-protein-biomarkers-for-burning-mouth-syndrome-discovered-by-quantitative-proteomics
#9
Eoon Hye Ji, Cynthia Diep, Tong Liu, Hong Li, Robert Merrill, Diana Messadi, Shen Hu
Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients' saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects ( p ≤ 0...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#10
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28317349/-gene-mutational-analyses-of-the-cathepsin-c-gene-in-families-with-papillon-lef%C3%A3-vre-syndrome
#11
Chen Yuanjiao, Li Chen-Jun
OBJECTIVE: This study aims to investigate the gene mutational characteristics of cathepsin C (CTSC) gene in a Chinese patient with Papillon-Lefèvre syndrome (PLS), then further confirm the genetic basis for the phenotype of PLS, and obtain genetic information that can be used as guide in the diagnosis and treatment of PLS. METHODS: With their consent, peripheral blood samples were obtained from the proband and his family members (his parents and older sister) for genomic DNA extraction...
August 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28301521/lysosomal-adaptation-how-cells-respond-to-lysosomotropic-compounds
#12
Shuyan Lu, Tae Sung, Nianwei Lin, Robert T Abraham, Bart A Jessen
Lysosomes are acidic organelles essential for degradation and cellular homoeostasis and recently lysosomes have been shown as signaling hub to respond to the intra and extracellular changes (e.g. amino acid availability). Compounds including pharmaceutical drugs that are basic and lipophilic will become sequestered inside lysosomes (lysosomotropic). How cells respond to the lysosomal stress associated with lysosomotropism is not well characterized. Our goal is to assess the lysosomal changes and identify the signaling pathways that involve in the lysosomal changes...
2017: PloS One
https://www.readbyqxmd.com/read/28298913/cathepsin-e-deficiency-ameliorates-graft-versus-host-disease-and-modifies-dendritic-cell-motility
#13
Jörg Mengwasser, Liane Babes, Steffen Cordes, Sarah Mertlitz, Katarina Riesner, Yu Shi, Aleixandria McGearey, Martina Kalupa, Thomas Reinheckel, Olaf Penack
Microbial products influence immunity after allogeneic hematopoietic stem cell transplantation (allo-SCT). In this context, the role of cathepsin E (Ctse), an aspartate protease known to cleave bacterial peptides for antigen presentation in dendritic cells (DCs), has not been studied. During experimental acute graft-versus-host disease (GVHD), we found infiltration by Ctse-positive immune cells leading to higher Ctse RNA- and protein levels in target organs. In Ctse-deficient allo-SCT recipients, we found ameliorated GVHD, improved survival, and lower numbers of tissue-infiltrating DCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28295446/a-recombinant-cystatin-from-ascaris-lumbricoides-attenuates-inflammation-of-dss-induced-colitis
#14
S Coronado, L Barrios, J Zakzuk, R Regino, V Ahumada, L Franco, Y Ocampo, L Caraballo
Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of dextran sodium sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library, we obtained a recombinant cystatin (rAl-CPI)...
March 10, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28270590/inhibition-of-mapk-erk-pathway-in%C3%A2-vivo-attenuates-aortic-valve-disease-processes-in-emilin1-deficient-mouse-model
#15
Charu Munjal, Anil G Jegga, Amy M Opoka, Ivan Stoilov, Russell A Norris, Craig J Thomas, J Michael Smith, Robert P Mecham, Giorgio M Bressan, Robert B Hinton
Aortic valve disease (AVD) is a common condition with a progressive natural history, and presently, there are no pharmacologic treatment strategies. Elastic fiber fragmentation (EFF) is a hallmark of AVD, and increasing evidence implicates developmental elastic fiber assembly defects. Emilin1 is a glycoprotein necessary for elastic fiber assembly that is present in both developing and mature human and mouse aortic valves. The Emilin1-deficient mouse (Emilin1(-/-) ) is a model of latent AVD, characterized by activated TGFβ/MEK/p-Erk signaling and upregulated elastase activity...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28253978/use-of-phlurorin-mkate2-human-lc3-to-monitor-autophagic-responses
#16
I Tanida, T Ueno, Y Uchiyama
In this chapter, we introduce the usage of pHluorin-mKate2-human LC3 for monitoring autophagy. Using EGFP and RFP, tandem fluorescent protein-tagged LC3 has been generated for monitoring autophagic structures. A critical point for this purpose is the sensitivity of the green fluorescent protein to acidic pH. A super-ecliptic pHluorin is most sensitive to acidic pH among EGFP, mWasabi, and pHluorin, indicating pHluorin is most suitable for monitoring autophagic structures. During autophagy, green-positive and red-positive fluorescent puncta of pHluorin-mKate2-human LC3 indicate signals of preautophagosomes and autophagosomes...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28251948/-peptide-drug-cortexin-inhibits-brain-caspase-8
#17
A A Yakovlev, A A Lyzhin, L G Khaspekov, A B Guekht, N V Gulyaeva
Cortexin, a drug containing hydrolyzed brain peptides, has long been used in clinics, but the mechanisms of its action remain obscure. We have hypothesized that cortexin-related neuroprotection is associated with the ability of the drug to inhibit brain proteases. Cortexin effectively inhibited brain caspase-8, while its effects on caspase-1, -3, -9, cathepsin B and calpain were much less pronounced or absent. In addition, we isolated a peptide fraction from cortexin holding all the inhibitory capacity of the original drug, but with a much more simple composition...
January 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28225025/specific-pathways-mediating-inflammasome-activation-by-candida-parapsilosis
#18
Adél Tóth, Erik Zajta, Katalin Csonka, Csaba Vágvölgyi, Mihai G Netea, Attila Gácser
Candida albicans and C. parapsilosis are human pathogens causing severe infections. The NLRP3 inflammasome plays a crucial role in host defence against C. albicans, but it has been previously unknown whether C. parapsilosis activates this complex. Here we show that C. parapsilosis induces caspase-1 activation and interleukin-1β (IL-1β) secretion in THP-1, as well as primary, human macrophages. IL-1β secretion was dependent on NLRP3, K(+)-efflux, TLR4, IRAK, Syk, caspase-1, caspase-8 and NADPH-oxidase. Importantly, while C...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#19
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28212734/role-of-granule-proteases-in-the-life-and-death-of-neutrophils
#20
REVIEW
Charaf Benarafa, Hans-Uwe Simon
Neutrophils constitute a crucial component of the innate immune defenses against microbes. Produced in the bone marrow and patrolling in blood vessels, neutrophils are recruited to injured tissues and are immediately active to contain pathogen invasion. Neutrophils undergo programmed cell death by multiple, context-specific pathways, which have consequences on immunopathology and disease outcome. Studies in the last decade indicate additional functions for neutrophils - or a subset of neutrophils - in modulating adaptive responses and tumor progression...
January 15, 2017: Biochemical and Biophysical Research Communications
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