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https://www.readbyqxmd.com/read/28640887/epidermal-growth-factor-promotes-cyclin-g2-degradation-via-calpain-mediated-proteolysis-in-gynaecological-cancer-cells
#1
Stefanie Bernaudo, Shahin Khazai, Eilyad Honarparvar, Alina Kopteva, Chun Peng
Cyclin G2 (CCNG2) is an atypical cyclin that functions to inhibit cell cycle progression and is often dysregulated in human cancers. We have previously shown that cyclin G2 is highly unstable and can be degraded through the ubiquitin/proteasome pathway. Furthermore, cyclin G2 contains a PEST domain, which has been suggested to act as a signal for degradation by multiple proteases. In this study, we determined if calpains, a family of calcium-dependent proteases, are also involved in cyclin G2 degradation. The addition of calpain inhibitors or silencing of calpain expression by siRNAs strongly enhanced cyclin G2 levels...
2017: PloS One
https://www.readbyqxmd.com/read/28637319/matrix-metalloproteinases-their-functional-role-in-lung-cancer
#2
Neha Merchant, Ganji Purnachandra Nagaraju, Balney Rajitha, Saipriya Lammata, Kishore Kumar Jella, Zachary S Buchwald, Sajani S Lakka, Arif N Ali
Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared to non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors which control the tumor microenvironment...
June 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28637209/purification-and-characterization-of-two-new-cell-bound-bioactive-compounds-produced-by-wildlactococcus-lactisstrain
#3
Margarete Alice Fontes Saraiva, Dag Anders Brede, Ingolf Figved Nes, Maria Cristina Baracat-Pereira, Marisa Vieira de Queiroz, Célia Alencar de Moraes
Novel compounds and innovative methods are required considering that antibiotic resistance has reached a crisis point. In the study, two cell-bound antimicrobial compounds produced by L. lactis ID1.5 were isolated and partially characterized. Following purification by cationic exchange and a solid phase C18 column, antimicrobial activity was recovered after three runs of RPC using 60% (v/v) and 100% (v/v) of 2-propanol for elution, suggesting that more than one antimicrobial compound were produced by L. lactis ID1...
June 20, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#4
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#5
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28636671/different-residues-in-the-sars-cov-spike-protein-determine-cleavage-and-activation-by-the-host-cell-protease-tmprss2
#6
Lennart Michel Reinke, Martin Spiegel, Teresa Plegge, Anika Hartleib, Inga Nehlmeier, Stefanie Gierer, Markus Hoffmann, Heike Hofmann-Winkler, Michael Winkler, Stefan Pöhlmann
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2...
2017: PloS One
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#7
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635647/virulence-genes-of-s-aureus-from-dairy-cow-mastitis-and-contagiousness-risk
#8
Giada Magro, Stefano Biffani, Giulietta Minozzi, Ralf Ehricht, Stefan Monecke, Mario Luini, Renata Piccinini
Staphylococcus aureus (S. aureus) is a major agent of dairy cow intramammary infections: the different prevalences of mastitis reported might be related to a combination of S. aureus virulence factors beyond host factors. The present study considered 169 isolates from different Italian dairy herds that were classified into four groups based on the prevalence of S. aureus infection at the first testing: low prevalence (LP), medium-low (MLP), medium-high (MHP) and high (HP). We aimed to correlate the presence of virulence genes with the prevalence of intramammary infections in order to develop new strategies for the control of S...
June 21, 2017: Toxins
https://www.readbyqxmd.com/read/28635289/exploring-the-drug-resistance-of-hcv-protease
#9
Garima Jindal, Dibyendu Mondal, Arieh Warshel
Hepatitis C virus (HCV) currently affects several million people across the globe. One of the major classes of drugs inhibits the NS3/4A protease of the polyprotein chain. Efficacy of these drugs is severely limited due to the high mutation rate that results in several genetically related quasispecies. The molecular mechanism of drug resistance is generally based on structural studies and binding free energies. However, prediction of new mutations requires a quantity that can define both binding free energy of the drug as well as the parameters (kcat and KM) for the natural substrate...
June 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28634118/identification-of-chickpea-seed-proteins-resistant-to-simulated-in-vitro-human-digestion
#10
I C Ribeiro, C C Leclercq, N Simões, A Toureiro, I Duarte, J B Freire, M M Chaves, J Renaut, C Pinheiro
Proteins and peptides able to resist gastrointestinal digestion and reach the intestinal mucosa have the potential to influence human health. Chickpea (Cicer arietinum L.) seed proteins are able to resist cooking (86.9% total protein) and/or in vitro simulated human digestion (15.9% total protein resists soaking, cooking and digestion with pepsin and pancreatin). To identify and characterize proteins resisting digestion we made use of different MS methodologies. The efficiency of several proteases (trypsin, AspN, chymotrypsin and LysC) was tested, and two technologies were employed (MALDI-TOF-TOF and LC-nESI-MS/MS)...
June 17, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28634061/isolation-of-a-protease-resistant-and-ph-stable-%C3%AE-galactosidase-displaying-hydrolytic-efficacy-toward-raffinose-family-oligosaccharides-from-the-button-mushroom-agaricus-bisporus
#11
Yujing Hu, Mengjuan Zhu, Guoting Tian, Liyan Zhao, Hexiang Wang, Tzi Bun Ng
A 45-kDa monomeric acidic α-galactosidase with a specific activity of 193.12 units/mg was isolated from the fruiting bodies of Agaricus bisporus. Blast search of internal peptide sequences suggested that it is a member of GH family 27 and it is most similar to hypothetical protein AGABI2DRAFT_70106. The enzyme displayed maximal activity at pH 4.0 and 60°C, respectively. The enzyme remained stable within the pH range 2.0-9.0 but its activity was markedly suppressed in the presence of Cu(2+), Hg(2+), Fe(3+) and Ag(+) ions...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28634057/evaluation-of-the-biotechnological-potential-of-a-novel-purified-protease-bs1-from-bacillus-safensis-s406-on-the-chitin-extraction-and-detergent-formulation
#12
Samiha Mhamdi, Intidhar Bkhairia, Rim Nasri, Tahar Mechichi, Moncef Nasri, Alya Sellami Kamoun
The aim of this study is the production of High-Added Value enzyme for Industrial Uses. An extracellular alkaline stable protease BS1 was purified from a newly bacterium, Bacillus safensis S406, isolated from the Sfax Solar Saltern. BS1 was purified by a process involving sulfate d'ammonium sulfate precipitation, sephadex G-75, Mono-Q anion-exchange chromatography and ultrafiltation. The enzyme has a molecular weight of 24kDa and appeared as a single band on native-PAGE. The optimum pH and temperature values of its proteolytic activity were pH 11...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28634018/distribution-subtype-population-and-ige-positivity-of-mast-cells-in-chronic-rhinosinusitis-with-nasal-polyps
#13
Shintaro Baba, Kenji Kondo, Maho Suzukawa, Ken Ohta, Tatsuya Yamasoba
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) has been categorized into 2 subtypes in the Asian population: eosinophilic chronic rhinosinusitis (ECRS; similar to CRSwNP in Western countries) and non-ECRS (characterized by inflammation dominated by T-helper cell type 1). The pathogenesis of CRSwNP and the role of mast cells are poorly understood. OBJECTIVE: To investigate the distribution, phenotypes, and immunoglobulin E (IgE) positivity of mast cells in these 2 subtypes of CRSwNP...
June 17, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28633877/epithelial-proteome-profiling-suggests-essential-role-of-interferon-inducible-proteins-in-allergic-rhinitis
#14
Joseph Ndika, Liisa Airaksinen, Hille Suojalehto, Piia Karisola, Nanna Fyhrquist, Anne Puustinen, Harri Alenius
BACKGROUND: Seasonal allergic rhinitis (SAR) as a result of intermittent exposure to seasonal pollen, causes itching, nasal congestion and repeated sneezing, with profound effects on the quality of life, work productivity and school performance. While both the genotype and environmental factors may contribute to the immunological basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear. METHODS: To address these questions, nasal epithelial brushings were collected from 29 SAR and 31 Control individuals during and after the pollen season...
June 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28633417/polypyrimidine-tract-binding-protein-ptb-and-ptb-associated-splicing-factor-in-cvb3-infection-an-itaf-for-an-itaf
#15
Pratik Dave, Biju George, Divya Khandige Sharma, Saumitra Das
The 5΄ UTR of Coxsackievirus B3 (CVB3) contains internal ribosome entry site (IRES), which allows cap-independent translation of the viral RNA and a 5΄-terminal cloverleaf structure that regulates viral replication, translation and stability. Here, we demonstrate that host protein PSF (PTB associated splicing factor) interacts with the cloverleaf RNA as well as the IRES element. PSF was found to be an important IRES trans acting factor (ITAF) for efficient translation of CVB3 RNA. Interestingly, cytoplasmic abundance of PSF protein increased during CVB3 infection and this is regulated by phosphorylation status at two different amino acid positions...
June 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28632940/characterization-of-the-i4399m-variant-of-apolipoprotein-a-implications-for-altered-prothrombotic-properties-of-lipoprotein-a
#16
Corey A Scipione, Jackson T McAiney, Daniel J Simard, Zainab A Bazzi, Matthew Gemin, Rocco Romagnuolo, Fraser L Macrae, Robert A Ariëns, Robert A Hegele, Janeen Auld, James W Gauld, Michael B Boffa, Marlys L Koschinsky
BACKGROUND: Lipoprotein(a) (Lp(a)) is a causal risk factor for a variety of cardiovascular diseases. Apolipoprotein(a) (apo(a)), the distinguishing component of Lp(a), is homologous to plasminogen, suggesting that Lp(a) can interfere with the normal fibrinolytic functions of plasminogen. This has implications for the persistence of fibrin clots in the vasculature and hence to atherothrombotic diseases. A single nucleotide polymorphism (rs3798220) in the gene encoding apo(a) has been reported that results in an Ile to Met substitution in the protease-like domain (I4399M variant)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#17
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632819/enzyme-development-for-human-islet-isolation-five-decades-of-progress-or-stagnation
#18
Daniel Brandhorst, Heide Brandhorst, Paul R V Johnson
In comparison to procedures used for the separation of individual cell types from other organs, the process of human pancreatic islet isolation aims to digest the pancreatic exocrine matrix completely without dispersing the individual cells within the endocrine cell cluster. This objective is unique within the field of tissue separation, and outlines the challenge of islet isolation to balance two opposing priorities. Although significant progress has been made in the characterization and production of enzyme blends for islet isolation, there are still numerous areas which require improvement...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632502/targeting-activated-protein-c-to-treat-hemophilia
#19
Stéphanie G I Polderdijk, Trevor P Baglin, James A Huntington
PURPOSE OF REVIEW: Hemophilia is a debilitating disease, marked by frequent, painful bleeding events, joint deterioration and early death. All current treatments consist of i.v. infusions of replacement factor or other procoagulant factors, and are incompletely effective, due in part to the short half-lives of the proteins. An alternative approach is to rebalance hemostasis by inhibiting natural anticoagulant mechanisms. In this article, we explain why activated protein C (APC) is an appropriate and safe target for the treatment of hemophilia...
June 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28632424/the-progress-in-the-research-of-antiplatelet-agents-1995-2017
#20
Oscar Benimana, Lulu Zhao, Yi Kong, Zhiyu Li, Zhouling Xie
Antiplatelet therapy displays a critical role in the treatment and prevention of antithrombotic disorders. Many new antiplatelet agents have been developed following the emergence of various clinical limitations of classical antiplatelet drugs. This review covers mainly the recent advances in the development of P2Y12 antagonists and GPIIb/IIIa antagonists. Meanwhile, it summarizes promising approaches to new platelet surface receptors such as prostanoid EP3 receptor, thromboxane A2 prostanoid receptor, protease-activated receptors, GPIb-IX-V receptor and P-selectin...
June 20, 2017: Future Medicinal Chemistry
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