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https://www.readbyqxmd.com/read/28323844/nuclear-localization-of-amyloid-%C3%AE-precursor-protein-binding-protein-fe65-is-dependent-on-regulated-intramembrane-proteolysis
#1
Niina A Koistinen, Anna K Edlund, Preeti K Menon, Elena V Ivanova, Smaranda Bacanu, Kerstin Iverfeldt
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65...
2017: PloS One
https://www.readbyqxmd.com/read/28302486/mitochondria-are-devoid-of-amyloid-%C3%AE-protein-a%C3%AE-producing-secretases-evidence-for-unlikely-occurrence-within-mitochondria-of-a%C3%AE-generation-from-amyloid-precursor-protein
#2
Naomi Mamada, Daisuke Tanokashira, Kazuhiro Ishii, Akira Tamaoka, Wataru Araki
Mitochondrial dysfunction is implicated in the pathological mechanism of Alzheimer's disease (AD). Amyloid β-protein (Aβ), which plays a central role in AD pathogenesis, is reported to accumulate within mitochondria. However, a question remains as to whether Aβ is generated locally from amyloid precursor protein (APP) within mitochondria. We investigated this issue by analyzing the expression patterns of APP, APP-processing secretases, and APP metabolites in mitochondria separated from human neuroblastoma SH-SY5Y cells and those expressing Swedish mutant APP...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28292959/multiepitope-tissue-analysis-reveals-sppl3-mediated-adam10-activation-as-a-key-step-in-the-transformation-of-melanocytes
#3
Christian Ostalecki, Jung-Hyun Lee, Jochen Dindorf, Lena Collenburg, Stephan Schierer, Beate Simon, Stefan Schliep, Elisabeth Kremmer, Gerold Schuler, Andreas S Baur
The evolution of cancer is characterized by the appearance of specific mutations, but these mutations are translated into proteins that must cooperate to induce malignant transformation. Using a systemic approach with the multiepitope ligand cartography (MELC) technology, we analyzed protein expression profiles (PEPs) in nevi and BRAF(V600E)-positive superficial spreading melanomas (SSMs) from patient tissues to identify key transformation events. The PEPs in nevi and SSMs differed predominantly in the abundance of specific antigens, but the PEPs of nevi- and melanoma-associated keratinocytes gradually changed during the transformation process...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28276471/meprin-metalloproteases-generate-biologically-active-soluble-interleukin-6-receptor-to-induce-trans-signaling
#4
Philipp Arnold, Inga Boll, Michelle Rothaug, Neele Schumacher, Frederike Schmidt, Rielana Wichert, Janna Schneppenheim, Juliane Lokau, Ute Pickhinke, Tomas Koudelka, Andreas Tholey, Björn Rabe, Jürgen Scheller, Ralph Lucius, Christoph Garbers, Stefan Rose-John, Christoph Becker-Pauly
Soluble Interleukin-6 receptor (sIL-6R) mediated trans-signaling is an important pro-inflammatory stimulus associated with pathological conditions, such as arthritis, neurodegeneration and inflammatory bowel disease. The sIL-6R is generated proteolytically from its membrane bound form and A Disintegrin And Metalloprotease (ADAM) 10 and 17 were shown to perform ectodomain shedding of the receptor in vitro and in vivo. However, under certain conditions not all sIL-6R could be assigned to ADAM10/17 activity. Here, we demonstrate that the IL-6R is a shedding substrate of soluble meprin α and membrane bound meprin β, resulting in bioactive sIL-6R that is capable of inducing IL-6 trans-signaling...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264989/characterization-of-the-catalytic-properties-of-the-membrane-anchored-metalloprotease-adam9-in-cell-based-assays
#5
Thorsten Maretzky, Steven Swendeman, Elin Mogollon, Gisela Weskamp, Umut Sahin, Karina Reiss, Carl P Blobel
ADAM9 (a disintegrin and metalloprotease9) is a membrane-anchored metalloproteinase that has been implicated in pathological retinal neovascularization and in tumor progression. ADAM9 has constitutive catalytic activity in both biochemical and cell-based assays and can cleave several membrane proteins, including Epidermal-Growth-Factor and Ephrin receptor B4. Yet, little is currently known about the catalytic properties of ADAM9 and its posttranslational regulation and inhibitor profile in cell-based assays...
March 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28249164/baff-and-taci-dependent-processing-of-baffr-by-adam-proteases-regulates-the-survival-of-b-cells
#6
Cristian R Smulski, Patrick Kury, Lea M Seidel, Hannah S Staiger, Anna K Edinger, Laure Willen, Maximilan Seidl, Henry Hess, Ulrich Salzer, Antonius G Rolink, Marta Rizzi, Pascal Schneider, Hermann Eibel
B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28216310/adamts-and-adam-metalloproteinases-in-osteoarthritis-looking-beyond-the-usual-suspects
#7
REVIEW
C-Y Yang, A Chanalaris, L Troeberg
INTRODUCTION: Matrix metalloproteinases (MMPs) and 'aggrecanase' a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix (ECM) type II collagen and aggrecan, and are thus potential targets for development of OA therapies. OBJECTIVE: This paper aims to provide a comprehensive review of the expression and potential roles of other, lesser-known ADAMTSs and related adamalysins (or a disintegrin and metalloproteinases (ADAMs)) in cartilage, with a view to identifying potentially protective or homoeostatic metalloproteinases in the joint and informing consequent selective inhibitor design...
February 13, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28216055/human-eosinophils-constitutively-express-a-unique-serine-protease-prss33
#8
Sumika Toyama, Naoko Okada, Akio Matsuda, Hideaki Morita, Hirohisa Saito, Takao Fujisawa, Susumu Nakae, Hajime Karasuyama, Kenji Matsumoto
BACKGROUND: Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis. METHODS: Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads...
February 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28196878/global-characterization-of-protein-secretion-from-human-macrophages-following-non-canonical-caspase-4-5-inflammasome-activation
#9
Martina B Lorey, Katriina Rossi, Kari K Eklund, Tuula A Nyman, Sampsa Matikainen
Gram-negative bacteria are associated with a wide spectrum of infectious diseases in humans. Inflammasomes are cytosolic protein complexes that are assembled when the cell encounters pathogens or other harmful agents. The non-canonical caspase-4/5 inflammasome is activated by gram-negative bacteria-derived lipopolysaccharide (LPS) and by endogenous oxidized phospholipids. Protein secretion is a critical component of the innate immune response. Here we have used label-free quantitative proteomics to characterize global protein secretion in response to non-canonical inflammasome activation upon intracellular LPS recognition in human primary macrophages...
February 14, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28184920/mir-365-targets-adam10-and-suppresses-the-cell-growth-and-metastasis-of-hepatocellular-carcinoma
#10
Yahui Liu, Wei Zhang, Songyang Liu, Kai Liu, Bai Ji, Yingchao Wang
Expression of miR-365 has been reported to be downregulated in hepatocellular carcinoma (HCC). However, the biological function and underlying mechanism of miR-365 in HCC growth and metastasis remain unclear. The aim of the present study was to explore the role of miR-365 in HCC progression. We found that miR-365 expression was downregulated in HCC tissues and cell lines. Further results showed that low expression of miR-365 was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28176357/bri2-processing-and-its-neuritogenic-role-are-modulated-by-protein-phosphatase-1-complexing
#11
Filipa Martins, Joana B Serrano, T Müller, Odete A B da Cruz E Silva, Sandra Rebelo
BRI2 is a ubiquitously expressed type-II transmembrane phosphoprotein. BRI2 undergoes proteolytic processing into secreted fragments and during the maturation process it suffers post-translational modifications. Of particular relevance, BRI2 is a protein phosphatase 1 (PP1) interacting protein, where PP1 is able to dephosphorylate the former. Further, disruption of the BRI2:PP1 complex, using BRI2 PP1 binding motif mutants, leads to increased BRI2 phosphorylation levels. However, the physiological function of BRI2 remains elusive; although findings suggest a role in neurite outgrowth and neuronal differentiation...
February 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28169407/neuron-derived-adam10-production-stimulates-peripheral-nerve-injury-induced-neuropathic-pain-by-cleavage-of-e-cadherin-in-satellite-glial-cells
#12
Jian Li, Qing Ouyang, Cheng-Wen Chen, Qian-Bo Chen, Xiang-Nan Li, Zheng-Hua Xiang, Hong-Bin Yuan
No abstract text is available yet for this article.
February 7, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28164773/apolipoprotein-e-mediated-modulation-of-adam10-in-alzheimer-s-disease
#13
Ben Shackleton, Fiona Crawford, Corbin Bachmeier
BACKGROUND: The APOE4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). It has been associated with an accumulation of amyloid-β (Aβ) in the brain, which is produced through the sequential cleavage of the amyloid-β precursor protein (AβPP) by β- and γ-secretases. Alternatively, AβPP is also cleaved by α-secretases such as A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). OBJECTIVE: While several studies have investigated the impact of apoE on β- and γ-secretase, interactions between apoE and α-secretases have not been fully examined...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28161636/diallyl-trisulfide-a-chemopreventive-agent-from-allium-vegetables-inhibits-alpha-secretases-in-breast-cancer-cells
#14
Violet A Kiesel, Silvia D Stan
Breast cancer affects one in eight women throughout the course of their lifetime creating a demand for novel prevention strategies against this disease. The Notch signaling pathway is often aberrantly activated in human malignancies including breast cancer. Alpha secretases, including ADAM (A Disintegrin and Metalloprotease) -10 and -17, are proteases that play a key role in the cleavage of cell surface molecules and subsequent ligand-mediated activation of Notch signaling pathway. High expression levels of ADAM10 and 17 have been clinically associated with a lower disease-free survival in breast cancer patients...
February 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28160627/interleukin-11-driven-gastric-tumourigenesis-is-independent-of-trans-signalling
#15
Jesse J Balic, Christoph Garbers, Stefan Rose-John, Liang Yu, Brendan J Jenkins
Deregulated gp130-dependent STAT3 signalling by the pleiotropic cytokine interleukin (IL)-11 has been implicated in the pathogenesis of gastric cancer (GC), the third most common cancer worldwide. While the IL-11-gp130-STAT3 signalling axis has traditionally been thought to exclusively use the membrane-bound IL-11 receptor (mIL-11R), recent evidence suggests that mIL-11R can be proteolytically cleaved to generate a soluble form (sIL-11R) which can elicit trans-signalling. Since the role of IL-11 trans-signalling in disease pathogenesis is unknown, here we have employed the IL-11-driven gp130(F/F) spontaneous model of GC to determine whether IL-11 trans-signalling promotes gastric tumourigenesis...
February 1, 2017: Cytokine
https://www.readbyqxmd.com/read/28158408/adam10-initiated-release-of-notch-intracellular-domain-regulates-microtubule-stability-and-radial-migration-of-cortical-neurons
#16
Zhi Yang, Peng-Fei Li, Ren-Chao Chen, Jie Wang, Shaoran Wang, Ya Shen, Xiaohui Wu, Bing Fang, Xuewen Cheng, Zhi-Qi Xiong
No abstract text is available yet for this article.
February 3, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28112644/pkc%C3%AE-links-proximal-t-cell-and-notch-signaling-through-localized-regulation-of-the-actin-cytoskeleton
#17
Graham J Britton, Rachel Ambler, Danielle J Clark, Elaine V Hill, Helen M Tunbridge, Kerrie E McNally, Bronwen R Burton, Philomena Butterweck, Catherine Sabatos-Peyton, Lea A Hampton-O'Neil, Paul Verkade, Christoph Wuelfing, David Cameron Wraith
Notch is a critical regulator of T cell differentiation and is activated through proteolytic cleavage in response to ligand engagement. Using murine myelin-reactive CD4 T cells, we demonstrate that proximal T cell signaling modulates Notch activation by a spatiotemporally constrained mechanism. The protein kinase PKCθ is a critical mediator of signaling by the T cell antigen receptor and the principal costimulatory receptor CD28. PKCθ selectively inactivates the negative regulator of F-actin generation, Coronin 1A, at the center of the T cell interface with the antigen presenting cell (APC)...
January 31, 2017: ELife
https://www.readbyqxmd.com/read/28107420/the-polyherbal-wattana-formula-displays-anti-amyloidogenic-properties-by-increasing-%C3%AE-secretase-activities
#18
Htut Htut Htoo, Suveerawan Limsuvan, Onusa Thamsermsang, Jean-François Hernandez, Frédéric Checler, Piyarat Govitrapong, Narawut Pakaprot, Pravit Akarasereenont, Bruno Vincent
Alzheimer's disease is characterized by the deposition of insoluble amyloid-β peptides produced from the β-amyloid precursor protein (βAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aβ, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression...
2017: PloS One
https://www.readbyqxmd.com/read/28106546/a-common-variant-of-il-6r-is-associated-with-elevated-il-6-pathway-activity-in-alzheimer-s-disease-brains
#19
Patrick C G Haddick, Jessica L Larson, Nisha Rathore, Tushar R Bhangale, Qui T Phung, Karpagam Srinivasan, David V Hansen, Jennie R Lill, Margaret A Pericak-Vance, Jonathan Haines, Lindsay A Farrer, John S Kauwe, Gerard D Schellenberg, Carlos Cruchaga, Alison M Goate, Timothy W Behrens, Ryan J Watts, Robert R Graham, Joshua S Kaminker, Marcel van der Brug
The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#20
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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