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https://www.readbyqxmd.com/read/27920432/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#1
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 2016: Scientific Reports
https://www.readbyqxmd.com/read/27918112/validation-of-adam10-metalloprotease-as-a-bacillus-thuringiensis-cry3aa-toxin-functional-receptor-in-colorado-potato-beetle-leptinotarsa-decemlineata
#2
V M Ruiz-Arroyo, I García-Robles, C Ochoa-Campuzano, G A Goig, E Zaitseva, G Baaken, A C Martínez-Ramírez, C Rausell, M D Real
Bacillus thuringiensis parasporal crystal proteins (Cry proteins) are insecticidal pore-forming toxins that bind to specific receptor molecules on the brush border membrane of susceptible insect midgut cells to exert their toxic action. In the Colorado potato beetle (CPB), a coleopteran pest, we previously proposed that interaction of Cry3Aa toxin with a CPB ADAM10 metalloprotease is an essential part of the mode of action of this toxin. Here, we annotated the gene sequence encoding an ADAM10 metalloprotease protein (CPB-ADAM10) in the CPB genome sequencing project, and using RNA interference gene silencing we demonstrated that CPB-ADAM10 is a Cry3Aa toxin functional receptor in CPB...
December 5, 2016: Insect Molecular Biology
https://www.readbyqxmd.com/read/27913191/the-shedding-derived-soluble-receptor-for-advanced-glycation-endproducts-sustains-inflammation-during-acute-pseudomonas-aeruginosa-lung-infection
#3
Antonella Antonelli, Stefania Di Maggio, Joanna Rejman, Francesca Sanvito, Alice Rossi, Alessandro Catucci, Andrea Gorzanelli, Alessandra Bragonzi, Marco E Bianchi, Angela Raucci
BACKGROUND: The membrane-bound isoform of the receptor for advanced glycation end products (FL-RAGE) is primarily expressed by alveolar epithelial cells and undergoes shedding by the protease ADAM10, giving rise to soluble cleaved RAGE (cRAGE). RAGE has been associated with the pathogenesis of several acute and chronic lung disorders. Whether the proteolysis of FL-RAGE is altered by a given inflammatory stimulus is unknown. Pseudomonas aeruginosa causes nosocomial infections in hospitalized patients and is the major pathogen associated with chronic lung diseases...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#4
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27894840/overexpression-of-mterf4-promotes-the-amyloidogenic-processing-of-app-by-inhibiting-adam10
#5
Xiao-Liang Wang, Qing Liu, Guo-Jun Chen, Mei-Ling Li, Yan-Hui Ding
Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ) peptide in the brain, which is produced by the proteolysis of β-amyloid precursor protein (APP). Recently, the mitochondrial transcription factor 4 (MTERF4), a member of the MTERF family, was implicated in regulating mitochondrial DNA transcription and directly in controlling mitochondrial ribosomal translation. The present study identified a novel role for MTERF4 in shifting APP processing toward the amyloidogenic pathway. The levels of MTERF4 protein were significantly increased in the hippocampus of APP/PS1 mice...
November 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27877078/activation-of-the-cxcl16-cxcr6-pathway-by-inflammation-contributes-to-atherosclerosis-in-patients-with-end-stage-renal-disease
#6
Ze Bo Hu, Yan Chen, Yu Xiang Gong, Min Gao, Yang Zhang, Gui Hua Wang, Ri Ning Tang, Hong Liu, Bi Cheng Liu, Kun Ling Ma
Background: Chronic inflammation plays a critical role in the progression of atherosclerosis (AS). This study aimed to determine the effects of the CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on cholesterol accumulation in the radial arteries of end-stage renal disease (ESRD) patients with concomitant microinflammation and to further investigate the potential effects of the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R). Methods: Forty-three ESRD patients were divided into the control group (n=17) and the inflamed group (n=26) based on plasma C-reactive protein (CRP) levels...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27865768/regulation-of-extrasynaptic-signaling-by-polysialylated-ncam-impact-for-synaptic-plasticity-and-cognitive-functions
#7
REVIEW
Hristo Varbanov, Alexander Dityatev
The activation of synaptic N-methyl-d-aspartate-receptors (NMDARs) is crucial for induction of synaptic plasticity and supports cell survival, whereas activation of extrasynaptic NMDARs inhibits long-term potentiation and triggers neurodegeneration. A soluble polysialylated form of the neural cell adhesion molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B-containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism result in impaired synaptic plasticity and learning, which could be repaired by reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or downstream signaling through RasGRF1 and p38 MAP kinase...
November 16, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27858713/protein-expression-of-bace1-is-downregulated-by-donepezil-in-alzheimer-s-disease-platelets
#8
Tamires Alves Sarno, Leda Leme Talib, Helena Passarelli Giroud Joaquim, Jessyka Maria de França Bram, Wagner Farid Gattaz, Orestes Vicente Forlenza
BACKGROUND: Abnormal amyloid-β protein precursor (AβPP) metabolism is a key feature of Alzheimer's disease (AD). Platelets contain most of the enzymatic machinery required for AβPP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, AβPP-related molecules in platelets may be regarded as peripheral markers of AD. OBJECTIVE: We sought to determine the protein expression of the AβPP secretases (ADAM10, BACE1, and PSEN1) and AβPP ratio in platelets of patients with mild or moderate AD compared to healthy controls...
November 14, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27837433/tlr4-mediated-galectin-1-production-triggers-epithelial-mesenchymal-transition-in-colon-cancer-cells-through-adam10-and-adam17-associated-lactate-production
#9
Ga Bin Park, Daejin Kim
Toll-like receptor 4 (TLR4) activation is a key contributor to the carcinogenesis of colon cancer. Overexpression of galectin-1 (Gal-1) also correlates with increased invasive activity of colorectal cancer. Lactate production is a critical predictive factor of risk of metastasis, but the functional relationship between intracellular lactate and Gal-1 expression in TLR4-activated colon cancer remains unknown. In this study, we investigated the underlying mechanism and role of Gal-1 in metastasis and invasion of colorectal cancer (CRC) cells after TLR4 stimulation...
November 12, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27829441/characterization-of-exosomal-release-in-bovine-endometrial-intercaruncular-stromal-cells
#10
Yong Qin Koh, Hassendrini N Peiris, Kanchan Vaswani, Sarah Reed, Gregory E Rice, Carlos Salomon, Murray D Mitchell
BACKGROUND: Cell-to-cell communication between the blastocyst and endometrium is critical for implantation. In recent years, evidence has emerged from studies in humans and several other animal species that exosomes are secreted from the endometrium and trophoblast cells and may play an important role in cell-to-cell communication maternal-fetal interface during early pregnancy. Exosomes are stable extracellular lipid bilayer vesicles that encapsulate proteins, miRNAs, and mRNAs, with the ability to deliver their cargo to near and distant sites, altering cellular function(s)...
November 9, 2016: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/27818272/tetraspanin-3-a-central-endocytic-membrane-component-regulating-the-expression-of-adam10-presenilin-and-the-amyloid-precursor-protein
#11
Lisa Seipold, Markus Damme, Johannes Prox, Björn Rabe, Petr Kasparek, Radislav Sedlacek, Hermann Altmeppen, Michael Willem, Barry Boland, Markus Glatzel, Paul Saftig
Despite existing knowledge about the role of the A Disintegrin and Metalloproteinase 10 (ADAM10) as the α-secretase involved in the non-amyloidogenic processing of the amyloid precursor protein (APP) and Notch signalling we have only limited information about its regulation. In this study, we have identified ADAM10 interactors using a split ubiquitin yeast two hybrid approach. Tetraspanin 3 (Tspan3), which is highly expressed in the murine brain and elevated in brains of Alzheimer´s disease (AD) patients, was identified and confirmed to bind ADAM10 by co-immunoprecipitation experiments in mammalian cells in complex with APP and the γ-secretase protease presenilin...
November 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27790089/proteomic-substrate-identification-for-membrane-proteases-in-the-brain
#12
REVIEW
Stephan A Müller, Simone D Scilabra, Stefan F Lichtenthaler
Cell-cell communication in the brain is controlled by multiple mechanisms, including proteolysis. Membrane-bound proteases generate signaling molecules from membrane-bound precursor proteins and control the length and function of cell surface membrane proteins. These proteases belong to different families, including members of the "a disintegrin and metalloprotease" (ADAM), the beta-site amyloid precursor protein cleaving enzymes (BACE), membrane-type matrix metalloproteases (MT-MMP) and rhomboids. Some of these proteases, in particular ADAM10 and BACE1 have been shown to be essential not only for the correct development of the mammalian brain, but also for myelination and maintaining neuronal connections in the adult nervous system...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27784219/serum-starvation-induces-bace1-processing-and-secretion
#13
Alexandra-Vasiliki Stavropoulou, Olga Mavrofrydi, Paul Saftig, Spiros Efthimiopoulos
β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1...
October 25, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27774114/the-disintegrin-metalloproteinases-adam10-and-adam17-are-upregulated-in-cutaneous-squamous-cell-carcinomas
#14
S-T Oh, A Stark, J Reichrath
No abstract text is available yet for this article.
January 2016: Dermato-endocrinology
https://www.readbyqxmd.com/read/27758746/-in-search-of-new-substrates-of-adam10
#15
Mirca Saurty, Romain Sanson, Rania Amrane, Eric Rubinstein
No abstract text is available yet for this article.
October 2016: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/27725873/long-noncoding-rna-malat1-promotes-uveal-melanoma-cell-growth-and-invasion-by-silencing-of-mir-140
#16
Lei Sun, Peng Sun, Qi-Ying Zhou, Xiangchun Gao, Qing Han
Increasing evidences have demonstrated that long noncoding RNAs (LncRNAs) play a significant role in the development of tumor. However, the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in uveal melanoma remains unknown. In this study, we demonstrated that the expression of MALAT1 was upregulated in the uveal melanoma tissues compared to normal tissues. Among them, MALAT1 was upregulated in 72% (18/25) uveal melanoma tissues compared to their paired normal tissues. Knockdown of MALAT1 suppressed uveal melanoma cell proliferation, colony information, invasion and migration...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27706571/effects-of-shenkangling-intervention-on-the-mapk-pathway-in-rats-with-doxorubicin-induced-nephropathy
#17
S Ai, Y Y Lin, J Zheng, C X Qiu, Y J Liu, X Lin
Shenkangling plays a role of Yishenhuoxue effect for the treatment of children with nephrotic syndrome. The aim of this study was to investigate the effects of Shenkangling intervention on the mitogen-activated protein kinase (MAPK) pathway in rats with Adriamycin-induced nephropathy (AN) and its underlying mechanism of action. Nephrosis was induced in healthy Sprague-Dawley rats by doxorubicin and the rats were untreated or treated with prednisone, simvastatin, Shenkangling, or a combination thereof. Using real-time PCR, the mRNA expression levels of Chemokine (C-X-C motif) ligand 16 (CXCL16), A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and ADAM17 in the renal tissues of these rats were found to be decreased by the various treatments compared to those in the untreated doxorubicin-induced nephrosis rats...
August 19, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27692848/changes-in-expressions-of-adam9-10-and-17-as-well-as-%C3%AE-secretase-activity-in-renal-cell-carcinoma
#18
Nuray Erin, Tümay İpekçi, Bahar Akkaya, İrem Hicran Özbudak, Mehmet Baykara
BACKGROUND: ADAM9, 10, and 17 are a class of disintegrins and metallproteinases with α-secretase activity. There are conflicting results regarding the role(s) of ADAM9, 10, and 17 in carcinogenesis, and only a few studies have examined their levels and cellular localization in renal cell carcinoma (RCC). Studies examining changes in α-secretase activity in RCC compared to enzymatic activity of the uninvolved kidney are lacking. METHOD: A cross-sectional study was conducted in 56 patients undergoing radical nephrectomy after the diagnosis of RCC...
September 28, 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27628319/expression-of-adam10-fas-fasl-and-soluble-fasl-in-patients-with-oral-squamous-cell-carcinoma-oscc-and-their-association-with-clinical-pathological-parameters
#19
José Sergio Zepeda-Nuño, Celia Guerrero-Velázquez, Susana Del Toro-Arreola, Natali Vega-Magaña, Julián Ángeles-Sánchez, Jesse Haramati, Ana L Pereira-Suárez, Miriam R Bueno-Topete
ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage...
September 14, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27618097/effects-of-folic-acid-on-secretases-involved-in-a%C3%AE-deposition-in-app-ps1-mice
#20
Tian Tian, Dong Bai, Wen Li, Guo-Wei Huang, Huan Liu
Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase...
2016: Nutrients
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