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https://www.readbyqxmd.com/read/28644439/activation-of-cell-surface-grp78-decreases-endoplasmic-reticulum-stress-and-neuronal-death
#1
Morgane Louessard, Isabelle Bardou, Eloïse Lemarchand, Audrey M Thiebaut, Jérôme Parcq, Jérôme Leprince, Anne Terrisse, Valérie Carraro, Pierre Fafournoux, Alain Bruhat, Cyrille Orset, Denis Vivien, Carine Ali, Benoit D Roussel
The unfolded protein response (UPR) is an endoplasmic reticulum (ER) -related stress conserved pathway that aims to protect cells from being overwhelmed. However, when prolonged, UPR activation converts to a death signal, which relies on its PERK-eIF2α branch. Overactivation of the UPR has been implicated in many neurological diseases, including cerebral ischaemia. Here, by using an in vivo thromboembolic model of stroke on transgenic ER stress-reporter mice and neuronal in vitro models of ischaemia, we demonstrate that ischaemic stress leads to the deleterious activation of the PERK branch of the UPR...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644007/cyclotides-as-tools-in-chemical-biology
#2
Simon J de Veer, Joachim Weidmann, David J Craik
Among the various molecules that plants produce for defense against pests and pathogens, cyclotides stand out as exceptionally stable and structurally unique. These ribosomally synthesized peptides are around 30 amino acids in size, and are stabilized by a head-to-tail cyclic peptide backbone and three disulfide bonds that form a cystine knot. They occur in certain plants of the Rubiaceae, Violaceae, Cucurbitaceae, Fabaceae, and Solanaceae families, with an individual plant producing up to hundreds of different cyclotides...
June 23, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#3
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28640008/brain-derived-neurotrophic-factor-propeptide-inhibits-proliferation-and-induces-apoptosis-in-c6-glioma-cells
#4
Bangkun Yang, Jun Qin, Ying Nie, Yong Li, Qianxue Chen
There are several forms of brain-derived neurotrophic factor (BDNF), the precursor of BDNF, mature BDNF, and BDNF propeptide. They exert different effects through different transmembrane receptor signaling systems. Precursor of BDNF is enzymatically cleaved, either by intracellular or by extracellular proteases, to generate mature BDNF and its propeptide (BDNF propeptide). The aim of this study was to evaluate the potential molecular mechanisms that underlie the inhibition of glioma cell growth by the BDNF propeptide...
June 21, 2017: Neuroreport
https://www.readbyqxmd.com/read/28637319/matrix-metalloproteinases-their-functional-role-in-lung-cancer
#5
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/28632424/the-progress-in-the-research-of-antiplatelet-agents-1995-2017
#6
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
https://www.readbyqxmd.com/read/28631887/thymic-stromal-lymphopoietin-is-expressed-in-human-corneal-stromal-cells-and-secreted-upon-protease-activated-receptor-1-activation
#7
Hongbo Yin, Yan Tian, Rongying Luo, Yingping Deng
Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7) like cytokine that triggers inflammatory responses through activating dendritic cell. It is demonstrated to be involved in a number of disorders, including cancer, gastrointestinal diseases, and autoimmune diseases. In addition, TSLP is also found to be able to induce itch sensation by directly activating the itch sensory neurons. The expression of human TSLP is detected in various tissues such as heart, liver, testis, and prostate. In this study, we report that TSLP was expressed in the human corneal stromal cells, the highly specialized cells that are critical for the function of the cornea...
June 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28631341/evaluation-of-flubendiamide-induced-mitochondrial-dysfunction-and-metabolic-changes-in-helicoverpa-armigera-hubner
#8
Bharat Nareshkumar, Shaik Mohammad Akbar, Hari Chand Sharma, Senigala K Jayalakshmi, Kuruba Sreeramulu
Phthalic acid diamide insecticides are the most effective insecticides used against most of the lepidopteran pests including Helicoverpa armigera, a polyphagous pest posing threat to several crops worldwide. The present studies were undertaken to understand different target sites and their interaction with insect ryanodine receptors (RyR). Bioassays indicated that flubendiamide inhibited the larval growth in dose-dependent manner with LD50 value of 0.72 μM, and at 0.8 μM larval growth decreased by about 88%...
June 20, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28630289/green-mamba-peptide-targets-type-2-vasopressin-receptor-against-polycystic-kidney-disease
#9
Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico A Stura, Laura Vera, Sabrina Sigismeau, Bernard Mouillac, Hélène Orcel, Steve Peigneur, Jan Tytgat, Laura Droctové, Fabrice Beau, Jerome Nevoux, Marc Lombès, Gilles Mourier, Edwin De Pauw, Denis Servent, Christiane Mendre, Ralph Witzgall, Nicolas Gilles
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits nanomolar affinity for the V2R without any activity on 155 other G-protein-coupled receptors or on 15 ionic channels. Mambaquaretin-1 is a full antagonist of the V2R activation pathways studied: cAMP production, beta-arrestin interaction, and MAP kinase activity...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630087/paucimannose-rich-n-glycosylation-of-spatiotemporally-regulated-human-neutrophil-elastase-modulates-its-immune-functions
#10
Ian Loke, Ole Østergaard, Niels H H Heegaard, Nicolle H Packer, Morten Thaysen-Andersen
Human neutrophil elastase (HNE) is an important N-glycosylated serine protease in the innate immune system, but the structure and immune-modulating functions of HNE N-glycosylation remain undescribed. Herein, LC-MS/MS-based glycan, glycopeptide and glycoprotein profiling were utilised to first determine the heterogeneous N-glycosylation of HNE purified from neutrophil lysates and then from isolated neutrophil granules of healthy individuals. The spatiotemporal expression of HNE during neutrophil activation and the biological importance of its N-glycosylation were also investigated using immunoblotting, cell surface capture, native MS, receptor interaction, protease inhibition, and bacteria growth assays...
June 19, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28630024/proteolytic-control-of-interleukin-11-and-interleukin-6-biology
#11
REVIEW
Juliane Lokau, Maria Agthe, Charlotte M Flynn, Christoph Garbers
Interleukin-11 (IL-11) and IL-6 are secreted glycoproteins which fulfill important homeostatic functions. Activation of target cells occurs via membrane-bound IL-11 and IL-6 receptors (IL-11R and IL-6R, respectively). Formation of IL-11/IL-11R and IL-6/IL-6R complexes triggers the recruitment of a homodimer of the ubiquitously expressed signal-transducing β-receptor gp130 (classic signaling). IL-11R and IL-6R can be shed by several proteases, albeit with different preferences and specificities, and these soluble receptors (sIL-11R and sIL-6R) act as agonists and can activate in principle all cells via gp130...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28629525/erythropoietin-regulation-by-angiotensin-ii
#12
Yong-Chul Kim, Ognoon Mungunsukh, Regina M Day
The renin-angiotensin system (RAS) is a key regulator of blood pressure and blood volume homeostasis. The RAS is primarily comprised of the precursor protein angiotensinogen and the two proteases, renin and angiotensin-converting enzyme (ACE). Angiotensin I (Ang I) is derived from angiotensinogen by renin, but appears to have no biological activity. In contrast, angiotensin II (Ang II) that has a variety of biological functions in the cells is converted from Ang I through removal of two-C-terminal residues by ACE...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28629170/egfr-and-egfrviii-promote-angiogenesis-and-cell-invasion-in-glioblastoma-combination-therapies-for-an-effective-treatment
#13
REVIEW
Stefanie Keller, Mirko H H Schmidt
Epidermal growth factor receptor (EGFR) and the mutant EGFRvIII are major focal points in current concepts of targeted cancer therapy for glioblastoma multiforme (GBM), the most malignant primary brain tumor. The receptors participate in the key processes of tumor cell invasion and tumor-related angiogenesis and their upregulation correlates with the poor prognosis of glioma patients. Glioma cell invasion and increased angiogenesis share mechanisms of the degradation of the extracellular matrix (ECM) through upregulation of ECM-degrading proteases as well as the activation of aberrant signaling pathways...
June 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28626366/current-developments-in-mobilization-of-hematopoietic-stem-and-progenitor-cells-and-their-interaction-with-niches-in-bone-marrow
#14
REVIEW
Rudolf Richter, Wolfgang Forssmann, Reinhard Henschler
The clinical application of hematopoietic stem and progenitor cells (HSPCs) has evolved from a highly experimental stage in the 1980s to a currently clinically established treatment for more than 20,000 patients annually who suffer from hematological malignancies and other severe diseases. Studies in numerous murine models have demonstrated that HSPCs reside in distinct niches within the bone marrow environment. Whereas transplanted HSPCs travel through the bloodstream and home to sites of hematopoiesis, HSPCs can be mobilized from these niches into the blood either physiologically or induced by pharmaceutical drugs...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28624806/targeting-the-tumor-promoting-microenvironment-in-met-amplified-nsclc-cells-with-a-novel-inhibitor-of-pro-hgf-activation
#15
Benjamin Y Owusu, Shantasia Thomas, Phanindra Venukadasula, Zhenfu Han, James W Janetka, Robert A Galemmo, Lidija Klampfer
Targeted therapeutic agents, such as inhibitors of epithelial growth factor receptor (EGFR), have transformed the management of non-small cell lung cancer (NSCLC) patients. MET-amplified NSCLC cells display resistance to EGFR-targeting agents, but are addicted to MET signaling for survival and proliferation and are sensitive to MET inhibition. However, responsive cancer cells invariably develop resistance to MET-targeted treatment.The tumor microenvironment plays a major role in resistance to anticancer therapy...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624438/the-metalloproteinase-adam10-a-useful-therapeutic-target
#16
REVIEW
Sebastian Wetzel, Lisa Seipold, Paul Saftig
Proteolytic cleavage represents a unique and irreversible posttranslational event regulating the function and half-life of many intracellular and extracellular proteins. The metalloproteinase ADAM10 has raised attention since it cleaves an increasing number of protein substrates close to the extracellular membrane leaflet. This "ectodomain shedding" regulates the turnover of a number of transmembrane proteins involved in cell adhesion and receptor signaling. It can initiate intramembrane proteolysis followed by nuclear transport and signaling of the cytoplasmic domain...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28623231/cry6aa1-a-bacillus-thuringiensis-nematocidal-and-insecticidal-toxin-forms-pores-in-planar-lipid-bilayers-at-extremely-low-concentrations-and-without-the-need-of-proteolytic-processing
#17
Eva Fortea, Vincent Lemieux, Léna Potvin, Vimbai Chikwana, Samantha Griffin, Thimothy Hey, David McCaskill, Kenneth Narva, Sek Yee Tan, Xiaoping Xu, Vincent Vachon, Jean-Louis Schwartz
Cry6Aa1 is a Bacillus thuringiensis (Bt) toxin active against nematodes and corn rootworm insects. Its 3-D molecular structure, which has been recently elucidated, is unique among those known for other Bt toxins. Typical three-domain Bt toxins permeabilise receptor-free planar lipid bilayers (PLBs) by forming pores at doses in the 1-50 μg/ml range. Solubilisation and proteolytic activation are necessary steps for PLB permeabilisation. In contrast to other Bt toxins, Cry6Aa1 formed pores in receptor-free bilayers at doses as low as 200 pg/ml in a wide range of pH (5...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28622293/sumo-triggered-ubiquitination-of-nr4a1-controls-macrophage-cell-death
#18
Long Zhang, Feng Xie, Juan Zhang, Peter Ten Dijke, Fangfang Zhou
Nuclear receptor NR4A1 has been implicated as a key regulator in a wide range of pathophysiological responses. As an immediate early response gene, NR4A1 can be rapidly and potently induced by a variety of stimuli. Its induction is followed by its rapid degradation, but the mechanism by which NR4A1 is degraded remains poorly understood. Here we show that nuclear receptor NR4A1 is sumoylated by SUMO2/3. Upon poly-SUMO modification, NR4A1 can be targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#19
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619369/mechanisms-of-atherosclerosis-and-cardiovascular-disease-in-antiphospholipid-syndrome-and-systemic-lupus-erythematosus-new-therapeutic-approaches
#20
REVIEW
Chary Lopez-Pedrera, M Ángeles Aguirre-Zamorano, Carlos Pérez-Sánchez
Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are 2 highly related autoimmune-rheumatic diseases associated with an increased risk of developing cardiovascular (CV) diseases. Despite the great progresses made in understanding the pathological mechanisms leading to CV diseases in those pathologies, there is still the unmet need to improve long term prognosis. CV diseases in SLE and APS is thought to happen as the result of a complex interaction between traditional CV risk factors, immune deregulation and disease activity, including the synergic effect of cytokines, chemokines, adipokines, proteases, autoantibodies, adhesion receptors, oxidative stress and a plethora of intracellular signalling molecules...
June 12, 2017: Medicina Clínica
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