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serin protease inhibitor

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https://www.readbyqxmd.com/read/28526008/cleavage-of-the-urokinase-receptor-upar-on-oral-cancer-cells-regulation-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-and-potential-effects-on-migration-and-invasion
#1
Synnove Norvoll Magnussen, Elin Hadler-Olsen, Daniela Elena Costea, Eli Berg, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Tuula Salo, Inigo Martinez-Zubiaurre, Jan-Olof Winberg, Lars Uhlin-Hansen, Gunbjorg Svineng
BACKGROUND: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28524452/subtilisin-like-proteases-in-plant-defence-the-past-the-present-and-beyond
#2
REVIEW
Joana Figueiredo, Marta Sousa Silva, Andreia Figueiredo
Subtilisin-like proteases (or subtilases) are a very diverse family of serine peptidases present in many organisms, but mostly in plants. With a broad spectrum of biological functions ranging from protein turnover and plant development to interactions with the environment, subtilases have been gaining more attention for their involvement in plant defence responses against the most diverse pathogens. On the last 5 years, the number of published studies associating plant subtilases with pathogen resistance and plant immunity increased tremendously...
May 19, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28522588/a-potential-mechanism-for-adc-induced-neutropenia-role-of-neutrophils-in-their-own-demise
#3
Hui Zhao, Sara Gulesserian, Maria Christina Malinao, Sathish Kumar-Ganesan, James Song, Mi Sook Chang, Melissa M Williams, Zhilan Zeng, Michael Mattie, Brian A Mendelsohn, David R Stover, Fernando Doñate
Neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs) and we aimed to elucidate the potential mechanism of this toxicity. To investigate if ADCs affect neutrophil production from bone marrow, an in vitro assay was developed in which hematopoietic stem cells (HSCs) were differentiated to neutrophils. Several antibodies against targets absent in HSCs and neutrophils were conjugated to MMAE via a cleavable valine-citrulline linker (vcMMAE-ADCs) or MMAF via a non-cleavable maleimidocaproyl linker (mcMMAF-ADCs), and their cytotoxicity was tested in the neutrophil differentiation assay...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522421/a-chymotrypsin-like-serine-protease-from-portunus-trituberculatus-involved-in-pathogen-recognition-and-amp-synthesis-but-not-required-for-prophenoloxidase-activation
#4
Hourong Liu, Yuan Liu, Chengwen Song, Zhaoxia Cui
Clip domain serine proteases (clip-SPs) play critical roles in various immune responses in arthropods, such as hemolymph coagulation, antimicrobial peptide (AMP) synthesis, cell adhesion and melanization. In the present study, we report the molecular and functional characterization of a clip domain serine protease (PtcSP2) from the swimming crab Portunus trituberculatus. The N-terminal clip domain and the C-terminal SP-like domain of PtcSP2 were expressed in Escherichia coli system, and assayed for their activities...
May 15, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28521467/upregulation-of-maspin-expression-in-human-cervical-carcinoma-cells-by-transforming-growth-factor-%C3%AE-1-through-the-convergence-of-smad-and-non-smad-signaling-pathways
#5
Ariyaphong Wongnoppavich, Nahathai Dukaew, Sirinthip Choonate, Kongthawat Chairatvit
Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factor β1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514117/tailored-ahp-cyclodepsipeptides-as-potent-non-covalent-serine-protease-inhibitors
#6
Steffen Köcher, Juliana Rey, Jens Bongard, Andre N Tiaden, Michael Meltzer, Peter Richards, Michael Ehrmann, Markus Kaiser
The S1 serine protease family is one of the largest and biologically relevant protease families. Despite their biomedical significance, generic approaches to generate potent, class-specific, bioactive non-covalent inhibitors for these enzymes are still limited. Here, we demonstrate that Ahp-cyclodepsipeptides represent a suitable scaffold for generating target-tailored serine protease inhibitors. For efficient synthetic access, we developed a practical mixed solid and solution phase synthesis that we validated by the first chemical synthesis of two natural products, Tasipeptin A and B...
May 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28512253/infiltrating-myeloid-cells-exert-pro-tumorigenic-actions-via-neutrophil-elastase
#7
Irina Lerman, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Luis Chiriboga, Chunliu Pan, Kent L Nastiuk, John J Krolewski, Aritro Sen, Stephen R Hammes
Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer (PCa) and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here it is reported that granulocytic myeloid-derived suppressor cells (MDSCs) are the predominant tumor infiltrating cells in PCa xenografts established in athymic nude mice...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28501974/proteolytic-activities-in-cortex-of-apical-parts-of-vicia-faba-ssp-minor-seedling-roots-during-kinetin-induced-programmed-cell-death
#8
Andrzej Kaźmierczak, Magdalena Doniak, Anita Kunikowska
Programmed cell death (PCD) is a crucial process in plant development. In this paper, proteolytically related aspects of kinetin-induced PCD in cortex cells of Vicia faba ssp. minor seedlings were examined using morphological, fluorometric, spectrophotometric, and fluorescence microscopic analyses. Cell viability estimation after 46 μM kinetin treatment of seedling roots showed that the number of dying cortex cells increased with treatment duration, reaching maximum after 72 h. Weight of the apical root segments increased with time and was about 2...
May 13, 2017: Protoplasma
https://www.readbyqxmd.com/read/28496990/mtorc1-regulates-mannose-6-phosphate-receptor-transport-and-t-cell-vulnerability-to-regulatory-t-cells-by-controlling-kinesin-kif13a
#9
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28493964/non-human-primate-orthologues-of-tmprss2-cleave-and-activate-the-influenza-virus-hemagglutinin
#10
Pawel Zmora, Paulina Molau-Blazejewska, Stephanie Bertram, Kerstin Walendy-Gnirß, Inga Nehlmeier, Anika Hartleib, Anna-Sophie Moldenhauer, Sebastian Konzok, Susann Dehmel, Katherina Sewald, Constantin Brinkmann, Christoph Curths, Sascha Knauf, Jens Gruber, Kerstin Mätz-Rensing, Franziska Dahlmann, Armin Braun, Stefan Pöhlmann
The cellular serine protease TMPRSS2, a member of the type II transmembrane serine protease (TTSP) family, cleaves and activates the hemagglutinin of influenza A viruses (FLUAV) in cell culture and is essential for spread of diverse FLUAV in mice. Non-human primates (NHP), in particular rhesus and cynomolgus macaques, serve as animal models for influenza and experimental FLUAV infection of common marmosets has recently also been reported. However, it is currently unknown whether the NHP orthologues of human TMPRSS2 cleave and activate FLUAV hemagglutinin and contribute to viral spread in respiratory tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28473832/how-escherichia-coli-circumvent-complement-mediated-killing
#11
REVIEW
Afonso G Abreu, Angela S Barbosa
Complement is a crucial arm of the innate immune response against invading bacterial pathogens, and one of its main functions is to recognize and destroy target cells. Similar to other pathogens, Escherichia coli has evolved mechanisms to overcome complement activation. It is well known that capsular polysaccharide may confer resistance to complement-mediated killing and phagocytosis, being one of the strategies adopted by this bacterium to survive in serum. In addition, proteases produced by E. coli have been shown to downregulate the complement system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28472998/in-silico-prioritization-and-further-functional-characterization-of-spink1-intronic-variants
#12
Wen-Bin Zou, Hao Wu, Arnaud Boulling, David N Cooper, Zhao-Shen Li, Zhuan Liao, Jian-Min Chen, Claude Férec
BACKGROUND: SPINK1 (serine protease inhibitor, kazal-type, 1), which encodes human pancreatic secretory trypsin inhibitor, is one of the most extensively studied genes underlying chronic pancreatitis. Recently, based upon data from qualitative reverse transcription-PCR (RT-PCR) analyses of transfected HEK293T cells, we concluded that 24 studied SPINK1 intronic variants were not of pathological significance, the sole exceptions being two canonical splice site variants (i.e., c.87 + 1G > A and c...
May 4, 2017: Human Genomics
https://www.readbyqxmd.com/read/28471365/structural-features-of-ns3-of-dengue-virus-serotypes-2-and-4-in-solution-and-insight-into-rna-binding-and-the-inhibitory-role-of-quercetin
#13
Ankita Pan, Wuan Geok Saw, Malathy Sony Subramanian Manimekalai, Ardina Grüber, Shin Joon, Tsutomu Matsui, Thomas M Weiss, Gerhard Grüber
Dengue virus (DENV), which has four serotypes (DENV-1 to DENV-4), is the causative agent of the viral infection dengue. DENV nonstructural protein 3 (NS3) comprises a serine protease domain and an RNA helicase domain which has nucleotide triphosphatase activities that are essential for RNA replication and viral assembly. Here, solution X-ray scattering was used to provide insight into the overall structure and flexibility of the entire NS3 and its recombinant helicase and protease domains for Dengue virus serotypes 2 and 4 in solution...
May 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28467378/molecular-mechanism-of-quorum-sensing-in-enterococcus-faecalis-its-role-in-virulence-and-therapeutic-approaches
#14
REVIEW
Liaqat Ali, Mohsan Ullah Goraya, Yasir Arafat, Muhammad Ajmal, Ji-Long Chen, Daojin Yu
Quorum-sensing systems control major virulence determinants in Enterococcusfaecalis, which causes nosocomial infections. The E. faecalis quorum-sensing systems include several virulence factors that are regulated by the cytolysin operon, which encodes the cytolysin toxin. In addition, the E. faecalis Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models...
May 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28464560/matriptase-induces-metalloproteinase-dependent-aggrecanolysis-in-vitro-and-in-vivo-multiple-mechanisms-promote-cartilage-damage-in-osteoarthritis
#15
David J Wilkinson, Angela Habgood, Heather K Lamb, Paul Thompson, Alastair R Hawkins, Antoine Désilets, Richard Leduc, Torsten Steinmetzer, Maya Hammami, Melody S Lee, Charles S Craik, Sharon Watson, Hua Lin, Jennifer M Milner, Andrew D Rowan
Objectives To assess the ability of the type II transmembrane serine proteinase matriptase to promote aggrecan loss from cartilage of osteoarthritis (OA) patients, and whether matriptase inhibition could prevent aggrecan loss and cartilage damage in experimental OA. Methods Aggrecan release was assessed from human OA cartilage explants and human stem cell-derived cartilage discs, whilst cartilage conditioned media were used for western blotting. Gene expression was analysed by real-time PCR. Murine OA was induced by surgical destabilisation of the medial meniscus, and matriptase inhibitors delivered via osmotic mini-pump or intra-articular injection...
May 2, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28462021/differential-transcript-profile-of-inhibitors-with-potential-anti-venom-role-in-the-liver-of-juvenile-and-adult-bothrops-jararaca-snake
#16
Cícera Maria Gomes, Karen de Morais-Zani, Stephen Lu, Diego de Souza Buarque, Glória Regina Cardoso Braz, Kathleen Fernandes Grego, Aparecida Sadae Tanaka, Anita Mitico Tanaka-Azevedo
BACKGROUND: Snakes belonging to the Bothrops genus are vastly distributed in Central and South America and are responsible for most cases of reported snake bites in Latin America. The clinical manifestations of the envenomation caused by this genus are due to three major activities-proteolytic, hemorrhagic and coagulant-mediated by metalloproteinases, serine proteinases, phospholipases A2 and other toxic compounds present in snake venom. Interestingly, it was observed that snakes are resistant to the toxic effects of its own and other snake's venoms...
2017: PeerJ
https://www.readbyqxmd.com/read/28461310/structure-of-ev71-3c-pro-in-complex-with-nk-1-8k-indications-for-the-development-of-anti-enterovirus-protease-inhibitor
#17
Yaxin Wang, Lin Cao, Yangyang Zhai, Zheng Yin, Yuna Sun, Luqing Shang
Hand-foot-and-mouth disease (HFMD) caused by enterovirus is a threat to public health in worldwide. Up-to-date, enterovirus 71 (EV71) becomes one of the major causative agents of HFMD in Pacific-Asia region and causes millions of infections from its outbreak. However, no drug is currently available for clinical therapeutics. In our previous works, we developed a set of protease inhibitors (PIs) targeting EV71 3C(pro), among which NK-1.8k and NK-1.9k with various active group have high potency and selectivity...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28460881/rhomboid-proteases-in-human-disease-mechanisms-and-future-prospects
#18
REVIEW
Stefan Düsterhöft, Ulrike Künzel, Matthew Freeman
Rhomboids are intramembrane serine proteases that cleave the transmembrane helices of substrate proteins, typically releasing luminal/extracellular domains from the membrane. They are conserved in all branches of life and there is a growing recognition of their association with a wide range of human diseases. Human rhomboids, for example, have been implicated in cancer, metabolic disease and neurodegeneration, while rhomboids in apicomplexan parasites appear to contribute to their invasion of host cells. Recent advances in our knowledge of the structure and the enzyme function of rhomboids, and increasing efforts to identify specific inhibitors, are beginning to provide important insight into the prospect of rhomboids becoming future therapeutic targets...
April 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28459807/the-plant-defense-and-pathogen-counterdefense-mediated-by-hevea-brasiliensis-serine-protease-hbspa-and-phytophthora-palmivora-extracellular-protease-inhibitor-ppepi10
#19
Kitiya Ekchaweng, Edouard Evangelisti, Sebastian Schornack, Miaoying Tian, Nunta Churngchow
Rubber tree (Hevea brasiliensis Muell. Arg) is an important economic crop in Thailand. Leaf fall and black stripe diseases caused by the aggressive oomycete pathogen Phytophthora palmivora, cause deleterious damage on rubber tree growth leading to decrease of latex production. To gain insights into the molecular function of H. brasiliensis subtilisin-like serine proteases, the HbSPA, HbSPB, and HbSPC genes were transiently expressed in Nicotiana benthamiana via agroinfiltration. A functional protease encoded by HbSPA was successfully expressed in the apoplast of N...
2017: PloS One
https://www.readbyqxmd.com/read/28459663/does-evolocumab-as-a-pcsk9-inhibitor-ameliorate-the-lipid-profile-in-familial-hypercholesterolemia-patients-a-meta-analysis-of-randomized-controlled-trials
#20
Seyyed Majid Eslami, Shekoufeh Nikfar, Maryam Ghasemi, Mohammad Abdollahi
Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a member of regulatory serine proteases which is mostly expressed in liver. In the physiological condition, LDL-C binds to LDL receptors (LDLRs) and via endocytosis, LDLRs are degraded. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of extracellular LDLRs, and then physiological recycling of LDLRs from surface of liver is cancelled, resulting in elevation of circulating LDL-C in plasma. To evaluate whether evolucomab, as PCSK9 inhibitor monoclonal antibody, ameliorates lipid profile in familial hypercholesterolemia (FH) patients, this meta-analysis has been conducted...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
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