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https://www.readbyqxmd.com/read/28819788/insulin-like-growth-factor-1-activates-different-catalytic-subunits-p110-of-pi3k-in-a-cell-type-dependent-manner-to-induce-lipogenesis-dependent-epithelial-mesenchymal-transition-through-the-regulation-of-adam10-and-adam17
#1
Ga Bin Park, Daejin Kim
The activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is critical for the induction of epithelial-mesenchymal transition (EMT) by growth factors, including insulin-like growth factor 1 (IGF-1). The activation of intracellular lipogenesis provides proliferative and survival signals for cancer cells. In this study, we investigated the connection between lipogenesis-related EMT processes and IGF-1-mediated PI3K p110 isoform activation in primary (SW480 cells) and metastatic (SW620) colon carcinoma cells...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28814605/adam10-mediated-icos-ligand-shedding-on-b-cells-is-necessary-for-proper-t-cell-icos-regulation-and-t-follicular-helper-responses
#2
Joseph C Lownik, Andrea J Luker, Sheela R Damle, Lauren Folgosa Cooley, Riham El Sayed, Andreas Hutloff, Costantino Pitzalis, Rebecca K Martin, Mohey Eldin M El Shikh, Daniel H Conrad
The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essential for maintaining proper immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant Ab production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that a disintegrin and metalloproteinase (ADAM)10 is the primary physiological sheddase of ICOSL in mice and humans. Using an in vivo system in which ADAM10 is deleted only on B cells, elevated levels of ICOSL were seen...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28801670/ectodomain-shedding-of-limbic-system-associated-membrane-protein-lsamp-by-adam-metallopeptidases-promotes-neurite-outgrowth-in-drg-neurons
#3
Ricardo L Sanz, Gino B Ferraro, Marie-Pier Girouard, Alyson E Fournier
IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs)...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745029/adam10-and-notch1-on-murine-dendritic-cells-control-the-development-of-type-2-immunity-and-ige-production
#4
Sheela R Damle, Rebecca K Martin, Chelsea L Cockburn, Joseph C Lownik, Jason A Carlyon, Allen D Smith, Daniel H Conrad
BACKGROUND: Allergy and allergic asthma are significant health burdens in developed countries and are increasing in prevalence. Dendritic cells (DCs) initiate immune responses to common aeroallergens and ADAM10 has been demonstrated to be important for the development of adaptive responses. This study's objective was to understand the role of ADAM10 on DCs in the development of allergic and anaphylactic responses. METHODS: In this study we used mouse models of allergic airway inflammation (house dust mice and Alternaria alternata) and OVA-induced models of active anaphylaxis to determine the DC-specific function of ADAM10 and Notch signaling...
July 26, 2017: Allergy
https://www.readbyqxmd.com/read/28739265/role-of-adam10-in-intestinal-crypt-homeostasis-and-tumorigenesis
#5
Peter J Dempsey
A disintegrin and metalloproteinases (ADAMs) are a family of mSultidomain, membrane-anchored proteases that regulate diverse cellular functions, including cell adhesion, migration, proteolysis and other cell signaling events. Catalytically-active ADAMs act as ectodomain sheddases that proteolytically cleave type I and type II transmembrane proteins and some GPI-anchored proteins from the cellular surface. ADAMs can also modulate other cellular signaling events through a process known as regulated intramembrane proteolysis (RIP)...
July 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28735867/cleavage-of-the-interleukin-11-receptor-induces-processing-of-its-c-terminal-fragments-by-the-gamma-secretase-and-the-proteasome
#6
Juliane Lokau, Charlotte M Flynn, Christoph Garbers
The cytokine Interleukin-11 (IL-11) signals through the membrane-bound IL-11 receptor (IL-11R), which is expressed in a cell-type specific manner. We have recently shown that the metalloprotease ADAM10 can cleave the IL-11R. The liberated soluble IL-11R (sIL-11R) ectodomain can bind its ligand, and the resulting IL-11/sIL-11R complex can activate cells that do not express the IL-11R (trans-signaling). In this study, we show that the remaining C-terminal fragment (CTF1) after ADAM10-mediated cleavage is subsequently cleaved within the membrane by the gamma-secretase complex, and that the resulting shorter CTF2 is further degraded by the proteasome...
July 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#7
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28732877/enhanced-antitumor-activity-of-gemcitabine-by-polysaccharide-induced-nk-cell-activation-and-immune-cytotoxicity-reduction-in-vitro-vivo
#8
Xin Xie, Yiran Zhou, Xue Wang, Jian Guo, Jingwen Li, Hongye Fan, Jie Dou, Baiyong Shen, Changlin Zhou
The polysaccharide SEP has been reported to activate NK and T cells via TLR2/4. Here, the combination of gemcitabine (GEM) and SEP against HepG-2 was investigated. SEP apparently enhanced antitumor activity of gemcitabine against liver cancer through stimulating NKG2D and DAP10/Akt pathway to activate NK cells. The NKG2D upregulation could improve the sensitivity of NK-92 cells targeting to its ligand MICA expressed on HepG-2 cells. Meanwhile, GEM up-regulated MICA expression and attenuated soluble MICA secretion through inhibiting ADAM10 expression, which in turn enhanced the cytotoxicity of NK-92 cells against cancer cells...
October 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28729535/pld1-promotes-dendritic-spine-development-by-inhibiting-adam10-mediated-n-cadherin-cleavage
#9
Li-Da Luo, Gang Li, Yun Wang
Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer's disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722189/adam10-modulates-calcitriol-regulated-rage-in-cardiomyocytes
#10
Ting-Wei Lee, Yu-Hsun Kao, Ting-I Lee, Yi-Jen Chen
BACKGROUND: Receptor for advanced glycation end products (RAGE) signalling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression. This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes. MATERIALS AND METHODS: Western blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N-terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL-1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor-κB (NF-κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 h...
July 19, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28707894/vitamin-d-receptor-regulates-amyloid-beta-1-42-production-with-protein-disulfide-isomerase-a3
#11
Duygu Gezen-Ak, Irem L Atasoy, Esin Candas, Merve Alaylioglu, Selma Yilmazer, Erdinc Dursun
The challenge of understanding the biology of neuronal amyloid processing could provide a basis for understanding the amyloid pathology in Alzheimer's disease (AD). Based on our previous studies we have suggested that AD might be the consequence of a hormonal imbalance in which the critical hormone is vitamin D. The present study primarily focused on the creation of a condition that prevents the genomic or non-genomic action of vitamin D by disrupting vitamin D receptors (VDR or PDIA3/1,25MARRS); the effects of these disruptions on the series of proteins involved in secretases that play a crucial role in amyloid pathology and on amyloid beta (Aβ) production in primary cortical neurons were observed...
July 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28703811/cytoplasmic-fragment-of-cd147-generated-by-regulated-intramembrane-proteolysis-contributes-to-hcc-by-promoting-autophagy
#12
Bo Wu, Jian Cui, Xiang-Min Yang, Zhen-Yu Liu, Fei Song, Ling Li, Jian-Li Jiang, Zhi-Nan Chen
Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers worldwide. CD147 (EMMPRIN or basigin) is a leading gene relating to hepatocarcinogenesis and metastasis, and is detected in transmembrane, exosome or circulating forms in HCC patients. The endosome recycling of CD147 further enhances the function of this oncoprotein from a dynamic perspective. However, previous studies about CD147 mainly focused on one separate form, and little attention has been paid to how the different forms of tumor-derived CD147 changes...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703301/the-xenoestrogens-biphenol-a-and-nonylphenol-differentially-regulate-metalloprotease-mediated-shedding-of-egfr-ligands
#13
Paulina Urriola-Muñoz, Xue Li, Thorsten Maretzky, David R McIlwain, Tak W Mak, Juan G Reyes, Carl P Blobel, Ricardo D Moreno
The xenoestrogens Bisphenol-A (BPA) and Nonylphenol (NP) are endocrine disruptors used in the plastic polymer industry to manufacture different products for human use. Previous studies have suggested a role of these compounds in the shedding of signaling molecules, such as tumor necrosis factor α (TNF- α). The aim of this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its newly discovered regulators iRhom1 and iRhom2 in the release of EGFR-ligands. We report that BPA and NP can stimulate the release of the ADAM17-substrates HB-EGF and TGF- α...
July 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28698968/inhibition-of-poly-adp-ribose-polymerase-1-enhances-gene-expression-of-selected-sirtuins-and-app-cleaving-enzymes-in-amyloid-beta-cytotoxicity
#14
Przemysław L Wencel, Walter J Lukiw, Joanna B Strosznajder, Robert Piotr Strosznajder
Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the regulation of cell metabolism, transcription, and DNA repair. Alterations of these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous results indicated that amyloid beta (Aβ) peptides and inflammation led to activation of PARP1 and cell death. This study focused on a role of PARP1 in the regulation of gene expression for SIRTs and beta-amyloid precursor protein (βAPP) cleaving enzymes under Aβ42 oligomers (AβO) toxicity in pheochromocytoma cells (PC12) in culture...
July 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28687716/regulation-of-the-trafficking-and-the-function-of-the-metalloprotease-adam10-by-tetraspanins
#15
REVIEW
Julien Saint-Pol, Etienne Eschenbrenner, Emmanuel Dornier, Claude Boucheix, Stéphanie Charrin, Eric Rubinstein
By interacting directly with partner proteins and with one another, tetraspanins organize a network of interactions referred to as the tetraspanin web. ADAM10 (A Disintegrin And Metalloprotease 10), an essential membrane-anchored metalloprotease that cleaves off the ectodomain of a large variety of cell surface proteins including cytokines, adhesion molecules, the precursor of the β-amyloid peptide APP or Notch, has emerged as a major component of the tetraspanin web. Recent studies have shown that ADAM10 associates directly with all members (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) of a subgroup of tetraspanins having eight cysteines in the large extracellular domain and referred to as TspanC8...
August 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28669545/retrograde-synaptic-inhibition-is-mediated-by-%C3%AE-neurexin-binding-to-the-%C3%AE-2%C3%AE-subunits-of-n-type-calcium-channels
#16
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M Kaplan
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/α2δ), decreasing UNC-36 abundance at pre-synaptic elements...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28656294/overexpression-of-a-disintegrin-and-metalloprotease-10-promotes-tumor-proliferation-migration-and-poor-prognosis-in-hypopharyngeal-squamous-cell-carcinoma
#17
Chuanjin Ding, Qicheng Zhang, Yan Chen, Xiaobo Zhang, Pei Wu, Zhenxin Zhang
The aim of this study was to determine the effect of A disintegrin and metalloprotease 10 (ADAM10) protein expression on the progression, migration and prognosis of hypopharyngeal squamous cell carcinoma (HSCC). Immunohistochemistry and western blot analysis were performed to detect ADAM10 expression in human HSCC specimens. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound-healing assay were employed to investigate the effects of ADAM10 knockdown (ADAM10-RNAi) on major oncogenic properties of FaDu cells...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28625569/synaptic-dysfunction-in-alzheimer-s-disease-from-the-role-of-amyloid-%C3%AE-peptide-to-the-%C3%AE-secretase-adam10
#18
Stefano Musardo, Elena Marcello
Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on patients, caregivers and society, it represents the largest unmet medical need in neurology, because it is currently incurable. In the last few years, the amyloid hypothesis, which points to amyloid β-peptide (Aβ) as the initiating factor in AD, had a central role in the development of therapeutic strategies for AD...
June 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28624438/the-metalloproteinase-adam10-a-useful-therapeutic-target
#19
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/28624437/the-plasma-membrane-penultimate-regulator-of-adam-sheddase-function
#20
REVIEW
Karina Reiss, Sucharit Bhakdi
BACKGROUND: ADAM10 and ADAM17 are the best characterized members of the ADAM (A Disintegrin and Metalloproteinase) - family of transmembrane proteases. Both are involved diverse physiological and pathophysiological processes. ADAMs are known to be regulated by posttranslational mechanisms. However, emerging evidence indicates that the plasma membrane with its unique dynamic properties may additionally play an important role in controlling sheddase function. SCOPE OF REVIEW: Membrane events that could contribute to regulation of ADAM-function are summarized...
June 14, 2017: Biochimica et Biophysica Acta
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