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https://www.readbyqxmd.com/read/28216310/adamts-and-adam-metalloproteinases-in-osteoarthritis-looking-beyond-the-usual-suspects
#1
REVIEW
Chun-Yao Yang, Anastasios Chanalaris, Linda Troeberg
INTRODUCTION: Matrix metalloproteinases and 'aggrecanase' ADAMTSs are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix 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 ADAMs) in cartilage, with a view to identifying potentially protective or homeostatic metalloproteinases in the joint and informing consequent selective inhibitor design...
February 12, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28216055/human-eosinophils-constitutively-express-a-unique-serine-protease-prss33
#2
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
#3
Martina B Lorey, Katariina 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28068334/two-paralogous-tetraspanins-tsp-12-and-tsp-14-function-with-the-adam10-metalloprotease-sup-17-to-promote-bmp-signaling-in-caenorhabditis-elegans
#15
Lin Wang, Zhiyu Liu, Herong Shi, Jun Liu
The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28068307/transitional-b-cells-commit-to-marginal-zone-b-cell-fate-by-taok3-mediated-surface-expression-of-adam10
#16
Hamida Hammad, Matthias Vanderkerken, Philippe Pouliot, Kim Deswarte, Wendy Toussaint, Karl Vergote, Lana Vandersarren, Sophie Janssens, Ioanna Ramou, Savvas N Savvides, Jody J Haigh, Rudi Hendriks, Manfred Kopf, Katleen Craessaerts, Bart de Strooper, John F Kearney, Daniel H Conrad, Bart N Lambrecht
Notch2 and B cell antigen receptor (BCR) signaling determine whether transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it is unknown how these pathways are related. We generated Taok3(-/-) mice, lacking the serine/threonine kinase Taok3, and found cell-intrinsic defects in the development of MZB but not FoB cells. Type 1 transitional (T1) B cells required Taok3 to rapidly respond to ligation by the Notch ligand Delta-like 1. BCR ligation by endogenous or exogenous ligands induced the surface expression of the metalloproteinase ADAM10 on T1 B cells in a Taok3-dependent manner...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28059830/2-deoxy-d-glucose-suppresses-the-migration-and-reverses-the-drug-resistance-of-colon-cancer-cells-through-adam-expression-regulation
#17
Ga B Park, Yoon H Chung, Daejin Kim
Cancer cell resistance to chemotherapy is associated with a poor prognosis. The compound 2-deoxy-D-glucose (2-DG) enhances the effect of chemotherapy against cancer cells lines in vitro and in vivo. However, its effect on the epithelial to mesenchymal transition (EMT) in drug-resistant cancer cells has not been fully elucidated. In this study, we investigated whether treatment of 5-fluorouracil or oxaliplatin-resistant colorectal cancer (CRC) cells with 2-DG suppressed their migratory activity and enhanced their susceptibility to chemotherapy...
January 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28059793/resveratrol-intervenes-in-the-cholesterol-and-isoprenoid-mediated-amyloidogenic-processing-of-a%C3%AE-pp-in-familial-alzheimer-s-disease
#18
Mohan Sathya, Ponnusamy Moorthi, Palanisamy Premkumar, Mahesh Kandasamy, Kesavan Swaminathan Jayachandran, Muthuswamy Anusuyadevi
Deterioration of cholesterol metabolism has recently been a frontier subject of investigation in the field of Alzheimer's disease (AD). Though amyloid-β protein precursor (AβPP) primes the pathological cascade, changes in cholesterol levels and its intermediates, geranyl geranyl pyrophosphate and farnesyl pyrophosphate, is expected to have a different consequence on AβPP processing and amyloid-β (Aβ) generation. However, the use of statins (HMG-COA reductase inhibitor) has been widely implicated in slowing down the pathogenic progression of AD, while the epidemiological reports on its biological effect remains controversial...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28050792/alpha-synuclein-alters-differently-gene-expression-of-sirts-parps-and-other-stress-response-proteins-implications-for-neurodegenerative-disorders
#19
J Motyl, P L Wencel, M Cieślik, R P Strosznajder, J B Strosznajder
Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. It's assumed that ASN plays an important role in the pathogenesis of Parkinson's and Alzheimer's disease. However, the molecular mechanism of ASN toxicity has not been elucidated. This study focused on the role of extracellular ASN (eASN) in regulation of transcription of sirtuins (Sirts) and DNA-bound poly(ADP-ribose) polymerases (PARPs) - proteins crucial for cells' survival/death. Our results indicate that eASN enhanced the free radicals level, decreased mitochondria membrane potential, cells viability and activated cells' death...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28017127/marginal-vitamin-a-deficiency-exacerbates-memory-deficits-following-a%C3%AE-1-42-injection-in-rats
#20
Jiaying Zeng, Tingyu Li, Ming Gong, Wei Jiang, Ting Yang, Jie Chen, Youxue Liu, Li Chen
BACKGROUND: Although clinical vitamin A deficiency (VAD), which is a public health problem throughout the developing world, has been well controlled, marginal vitamin A deficiency (MVAD) is far more prevalent, especially among pregnant women and preschool children in China. Increasing evidence suggests that VAD is involved in the pathogenesis of Alzheimer's disease (AD). However, whether MVAD, beginning early in life, increases the risk of developing AD has yet to be determined. OBJECTIVE: The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats...
23, 2016: Current Alzheimer Research
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