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https://www.readbyqxmd.com/read/28454261/clinical-significance-of-adam10-expression-in-laryngeal-carcinoma
#1
Bo You, Miao Gu, Xiaolei Cao, Xingyu Li, Si Shi, Ying Shan, Yiwen You
Recent findings suggest that upregulated a disintegrin and metalloproteinase (ADAM)10 expression participates in the progression of multiple types of cancer. However, the expression pattern and clinicopathological significance of ADAM10, and its potential prognostic role in laryngeal carcinoma remains to be explored. The present study firstly determined the significantly elevated expression status of ADAM10 protein and messenger RNA in laryngeal carcinoma tissues compared with that in adjacent non-tumor tissues by western blotting and reverse transcription-quantitative polymerase chain reaction analysis...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28449222/tspan33-is-expressed-in-transitional-and-memory-b-cells-but-is-not-responsible-for-high-adam10-expression
#2
César Augusto Pérez-Martínez, José Luis Maravillas-Montero, Iván Meza-Herrera, Felipe Vences-Catalán, Albert Zlotnik, Leopoldo Santos-Argumedo
Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion, and other cellular processes. TspanC8, a subfamily of tetraspanins, were found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we analyzed the pattern of expression of Tspan33 in B cells from healthy donors. We found Tspan33 expression in early and late stages of B cell development...
April 27, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28442704/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#3
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28437250/ionizing-radiation-reduces-adam10-expression-in-brain-microvascular-endothelial-cells-undergoing-stress-induced-senescence
#4
Lucinda S McRobb, Matthew J McKay, Jennifer R Gamble, Michael Grace, Vaughan Moutrie, Estevam D Santos, Vivienne S Lee, Zhenjun Zhao, Mark P Molloy, Marcus A Stoodley
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28428248/new-insights-into-the-tetraspanin-tspan5-using-novel-monoclonal-antibodies
#5
Julien Saint-Pol, Martine Billard, Emmanuel Dornier, Etienne Eschenbrenner, Lydia Danglot, Claude Boucheix, Stéphanie Charrin, Eric Rubinstein
Tspan5 is a member of a subgroup of tetraspanins referred to as TspanC8. These tetraspanins directly interact with the metalloprotease ADAM10, regulate its exit from the endoplasmic reticulum and subsequent trafficking, and differentially regulate its ability to cleave various substrates and activate Notch signaling. The study of Tspan5 has been limited by the lack of good antibodies. This study provides new insights into Tspan5 using new monoclonal antibodies (mAbs), including two mAbs recognizing both Tspan5 and the highly similar tetraspanin Tspan17...
April 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28427048/1-25-dihydroxyvitamin-d3-attenuates-the-effects-of-lipopolysaccharide-by-causing-adam10-dependent-ectodomain-shedding-of-toll-like-receptor-4
#6
Won Seok Yang, Jin Ju Kim, Nam Jeong Han, Eun Kyoung Lee, Su-Kil Park
BACKGROUND/AIMS: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits the effects of lipopolysaccharide (LPS) in human aortic endothelial cells. METHODS: Cellular signaling was explored by determination of protein abundance with Western blot, measurement of cytosolic Ca2+ concentration and immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10). RESULTS: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM-1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen-activated protein kinase (p38 MAPK)...
April 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28413720/direct-imaging-of-app-proteolysis-in-living-cells
#7
Niccoló Parenti, Ambra Del Grosso, Claudia Antoni, Marco Cecchini, Renato Corradetti, Francesco S Pavone, Martino Calamai
Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of Aβ peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. Aβ peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue...
2017: PeerJ
https://www.readbyqxmd.com/read/28413487/vandetanib-and-adam-inhibitors-synergistically-attenuate-the-pathological-migration-of-ebv-infected-retinal-pigment-epithelial-cells-by-regulating-the-vegf-mediated-mapk-pathway
#8
Daejin Kim, Hyun-Suk Ko, Ga Bin Park, Dae Young Hur, Yeong Seok Kim, Jae Wook Yang
The extracellular signals induced by vascular endothelial growth factor (VEGF) are implicated in choroidal neovascularization (CNV) and thus, are associated with vision-limiting complications in the human retina. Vandetanib is an oral anticancer drug that selectively inhibits the activities of VEGF receptor and epidermal growth factor receptor tyrosine kinase; however, the effects of vandetanib on VEGF in retinal pigment epithelial (RPE) cells have not yet been studied. In the present study, a combined treatment of vandetanib and a disintegrin and metalloproteinase (ADAM) protein inhibitors were used to assess the regulation of Epstein-Barr virus (EBV)-infected ARPE19 cells (ARPE19/EBV) migration as a model of CNV...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28409746/the-role-of-adam10-in-alzheimer-s-disease
#9
Xiang-Zhen Yuan, Sen Sun, Chen-Chen Tan, Jin-Tai Yu, Lan Tan
As a member of the A Disintegrin And Metalloproteinase (ADAM) family, ADAM10 has been identified as the constitutive α-secretase in the process of amyloid-β protein precursor (AβPP) cleavage and plays a critical role in reducing the generation of the amyloid-β (Aβ) peptides. Recent studies have demonstrated its beneficial role in alleviating the pathologic impairment in Alzheimer's disease (AD) both in vitro and in vivo. However, the role of ADAM10 in AD and the underlying molecular mechanisms are still not well established...
April 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28409157/ferulic-acid-suppresses-amyloid-%C3%AE-production-in-the-human-lens-epithelial-cell-stimulated-with-hydrogen-peroxide
#10
Noriaki Nagai, Sachiyo Kotani, Yu Mano, Akina Ueno, Yoshimasa Ito, Toshio Kitaba, Takumi Takata, Noriko Fujii
It is well known that oxidative stresses induce the production of amyloid β (Aβ) in the brain, lens, and retina, leading to age-related diseases. In the present study, we investigated the effects of ferulic acid on the Aβ levels in H2O2-stimulated human lens epithelial (HLE) SRA 01/04 cells. Three types of Aβ peptides (Aβ1-40, Aβ1-42, and Aβ1-43) were measured by ELISA, and the levels of mRNA for the expressed proteins related to Aβ production (APP, BACE1, and PS proteins) and degradation (ADAM10, NEP, and ECE1 proteins) were determined by quantitative real-time RT-PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28408220/first-insight-into-structure-activity-relationships-of-selective-meprin-%C3%AE-inhibitors
#11
Daniel Ramsbeck, Antje Hamann, Dagmar Schlenzig, Stephan Schilling, Mirko Buchholz
The astacin proteases meprin α and β are emerging drug targets for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease. However, there are only few inhibitors of both proteases reported to date. Starting from NNGH as lead structure, a detailed elaboration of the structure-activity relationship of meprin β inhibitors was performed, leading to compounds with activities in the lower nanomolar range. Considering the preference of meprin β for acidic residues in the P1' position, the compounds were optimized...
April 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28367112/regulation-of-alpha-secretase-adam10-in-vitro-and-in-vivo-genetic-epigenetic-and-protein-based-mechanisms
#12
REVIEW
Kristina Endres, Thomas Deller
ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons, responsible for cleaving APP in a non-amyloidogenic manner. This cleavage results in the production of a neuroprotective APP-derived fragment, APPs-alpha, and an attenuated production of neurotoxic A-beta peptides. An increase in ADAM10 activity shifts the balance of APP processing toward APPs-alpha and protects the brain from amyloid deposition and disease. Thus, increasing ADAM10 activity has been proposed an attractive target for the treatment of neurodegenerative diseases and it appears to be timely to investigate the physiological mechanisms regulating ADAM10 expression...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28358908/pharmacogenomics-study-on-cadherin-2-network-with-regard-to-hiv-infection-and-methadone-treatment-outcome
#13
Hsiang-Wei Kuo, Chia-Lung Shih, Jieh-Hen Tsung, Sheng-Wen Liu, Shih-Kai Chu, Hsin-Chou Yang, Hsiao-Hui Tsou, Zih-Hsiang Wang, Andrew C H Chen, Yu-Li Liu
Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study...
2017: PloS One
https://www.readbyqxmd.com/read/28357407/role-of-microrna-103a-targeting-adam10-in-abdominal-aortic-aneurysm
#14
Tong Jiao, Ye Yao, Bo Zhang, Da-Cheng Hao, Qing-Feng Sun, Jing-Bo Li, Chao Yuan, Bao Jing, Yun-Peng Wang, Hai-Yang Wang
MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337142/icariside-ii-effectively-reduces-spatial-learning-and-memory-impairments-in-alzheimer-s-disease-model-mice-targeting-beta-amyloid-production
#15
Lingli Yan, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Fei Li, Jingshan Shi, Qihai Gong
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28323844/nuclear-localization-of-amyloid-%C3%AE-precursor-protein-binding-protein-fe65-is-dependent-on-regulated-intramembrane-proteolysis
#16
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
#17
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...
April 29, 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
#18
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
#19
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-metalloproteinase-adam9-in-cell-based-assays
#20
Thorsten Maretzky, Steven Swendeman, Elin Mogollon, Gisela Weskamp, Umut Sahin, Karina Reiss, Carl P Blobel
ADAM9 (A Disintegrin And Metalloprotease 9) 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 post-translational regulation and inhibitor profile in cell-based assays...
April 13, 2017: Biochemical Journal
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