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https://www.readbyqxmd.com/read/28334432/uch-l1-containing-exosomes-mediate-chemotherapeutic-resistance-transfer-in-breast-cancer
#1
Kuan Ning, Teng Wang, Xu Sun, Pengfei Zhang, Yun Chen, Jian Jin, Dong Hua
BACKGROUND: Chemotherapy resistance has become a serious challenge in the treatment of breast cancer. Previous studies showed cells can transfer proteins, including those responsible for drug resistance to adjacent cells via exosomes. METHODS: The switches of drug resistance via exosomes transfer were assessed by CellTiter-Blue Viability assay, flow cytometry, and immunostaining analysis. Relative protein levels of Ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1), P-glycoprotein (P-gp), extracellular-signal regulated protein kinase1/2 (ERK1/2), and phospho-extracellular-signal regulated protein kinase1/2 (p-ERK1/2) were measured by Western blot...
March 23, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#2
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333280/hcg-activates-the-erk1-2-mitogen-activated-protein-kinase-pathway-in-human-endometrial-stromal-cells-transiently-increasing-the-progesterone-receptor-and-regulating-genes-associated-with-endometrial-receptivity
#3
Alejandro Tapia-Pizarro, Sebastián Archiles, Felipe Argandoña, Cecilia Valencia, Keyla Zavaleta, María Cecilia Johnson, Reinaldo González-Ramos, Luigi Devoto
STUDY QUESTION: How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? SUMMARY ANSWER: CG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cAMP (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. WHAT IS KNOWN ALREADY: hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors...
March 14, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28326171/large-scale-isolation-and-cytotoxicity-of-extracellular-vesicles-derived-from-activated-human-natural-killer-cells
#4
Ambrose Y Jong, Chun-Hua Wu, Jingbo Li, Jianping Sun, Muller Fabbri, Alan S Wayne, Robert C Seeger
Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28325957/heat-shock-protein-hsp27-secretion-by-ovarian-cancer-cells-is-linked-to-intracellular-expression-levels-occurs-independently-of-the-endoplasmic-reticulum-pathway-and-hsp27-s-phosphorylation-status-and-is-mediated-by-exosome-liberation
#5
Matthias B Stope, Gerd Klinkmann, Karoline Diesing, Dominique Koensgen, Martin Burchardt, Alexander Mustea
The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock...
2017: Disease Markers
https://www.readbyqxmd.com/read/28325836/fibronectins-containing-extradomain-a-or-b-enhance-osteoblast-differentiation-via-distinct-integrins
#6
Carla Sens, Katrin Huck, Stefan Pettera, Stephan Uebel, Guido Wabnitz, Markus Moser, Inaam A Nakchbandi
Fibronectin is a multidomain protein secreted by various cell types. It forms a network of fibers within the extracellular matrix, and impacts intracellular processes by binding to various molecules, primarily integrin receptors on the cells. Both the presence of several isoforms and the ability of the various domains and isoforms to bind to a variety of integrins result in a wide range of effects. In vivo findings suggest that fibronectin isoforms produced by the osteoblasts enhance their differentiation. Here we report that the isoform characterized by the presence of extra-domain A (EDA) activates α4β1 integrin and augments osteoblast differentiation...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28323621/smoc-can-act-as-both-an-antagonist-and-an-expander-of-bmp-signaling
#7
J Terrig Thomas, D Eric Dollins, Kristin R Andrykovich, Tehyen Chu, Brian G Stultz, Deborah A Hursh, Malcolm Moos
The matricellular protein SMOC (Secreted Modular Calcium binding protein) is conserved phylogenetically from vertebrates to arthropods. We showed previously that SMOC inhibits bone morphogenetic protein (BMP) signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In contrast, the most prominent effect of the Drosophila orthologue, pentagone (pent), is expanding the range of BMP signaling during wing patterning. Using SMOC deletion constructs we found that SMOC-∆EC, lacking the extracellular calcium binding (EC) domain, inhibited BMP2 signaling, whereas SMOC-EC (EC domain only) enhanced BMP2 signaling...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28322247/tricyclic-antidepressants-promote-ceramide-accumulation-to-regulate-collagen-production-in-human-hepatic-stellate-cells
#8
Jennifer Y Chen, Benjamin Newcomb, Chan Zhou, Joshua V Pondick, Sarani Ghoshal, Samuel R York, Daniel L Motola, Nicolas Coant, Jae Kyo Yi, Cungui Mao, Kenneth K Tanabe, Irina Bronova, Evgeny V Berdyshev, Bryan C Fuchs, Yusuf Hannun, Raymond T Chung, Alan C Mullen
Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321417/technologies-for-proteome-wide-discovery-of-extracellular-host-pathogen-interactions
#9
REVIEW
Nadia Martinez-Martin
Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28319728/modulation-of-host-cell-apoptotic-pathways-by-intracellular-pathogens
#10
REVIEW
Anja Friedrich, Julian Pechstein, Christian Berens, Anja Lührmann
Nearly all steps of the host cell apoptotic cascade can be subverted by intracellular microorganisms. Some pathogens modulate early steps and interfere with sensing of extracellular signals, cellular stress or signal transduction; others target Bcl-2 proteins, caspases, or inhibitor of apoptosis proteins (IAPs). In many cases the exact molecular mechanisms leading to interference with the host cell apoptotic cascade are still unknown. However, there are some examples where bacterial factors that modulate host cell death have been identified...
March 17, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28319050/extracellular-matrix-proteomics-identifies-molecular-signature-of-symptomatic-carotid-plaques
#11
Sarah R Langley, Karin Willeit, Athanasios Didangelos, Ljubica Perisic Matic, Philipp Skroblin, Javier Barallobre-Barreiro, Mariette Lengquist, Gregor Rungger, Alexander Kapustin, Ludmilla Kedenko, Chris Molenaar, Ruifang Lu, Temo Barwari, Gonca Suna, Xiaoke Yin, Bernhard Iglseder, Bernhard Paulweber, Peter Willeit, Joseph Shalhoub, Gerard Pasterkamp, Alun H Davies, Claudia Monaco, Ulf Hedin, Catherine M Shanahan, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms. METHODS: We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318884/udp-p2y6-receptor-signaling-regulates-ige-dependent-degranulation-in-human-basophils
#12
Manabu Nakano, Koichi Ito, Takeo Yuno, Nobuyuki Soma, Syun Aburakawa, Kosuke Kasai, Toshiya Nakamura, Hideki Takami
BACKGROUND: P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca(2+) release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils...
March 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28317948/local-remodeling-of-synthetic-extracellular-matrix-microenvironments-by-co-cultured-endometrial-epithelial-and-stromal-cells-enables-long-term-dynamic-physiological-function
#13
Christi D Cook, Abby S Hill, Margaret Guo, Linda Stockdale, Julia P Papps, Keith B Isaacson, Douglas A Lauffenburger, Linda G Griffith
Mucosal barrier tissues, comprising a layer of tightly-bonded epithelial cells in intimate molecular communication with an underlying matrix-rich stroma containing fibroblasts and immune cells, are prominent targets for drugs against infection, chronic inflammation, and other disease processes. Although human in vitro models of such barriers are needed for mechanistic studies and drug development, differences in extracellular matrix (ECM) needs of epithelial and stromal cells hinder efforts to create such models...
March 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#14
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315083/achieving-the-promise-of-therapeutic-extracellular-vesicles-the-devil-is-in-details-of-therapeutic-loading
#15
REVIEW
Dhruvitkumar S Sutaria, Mohamed Badawi, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells...
March 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28314761/hypoxia-mediated-regulation-of-the-secretory-properties-of-mitral-valve-interstitial-cells
#16
Kareem Salhiyyah, Padmini Sarathchandra, Najma Latif, Magdi H Yacoub, Adrian H Chester
The sophisticated function of the mitral valve depends to a large extent on the extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important pathway is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVIC) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulphated glycosaminoglycans (sGAG) in cultured porcine MVIC...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28301987/properties-of-epithelial-cells-and-vaginal-secretions-in-pregnant-women-when-lactobacillus-crispatus-or-lactobacillus-iners-dominate-the-vaginal-microbiome
#17
Julie Leizer, Dimitrios Nasioudis, Larry J Forney, G Maria Schneider, Karol Gliniewicz, Allison Boester, Steven S Witkin
OBJECTIVE: Our objective was to determine differences in properties of vaginal epithelial cells and the composition of vaginal secretions when Lactobacillus crispatus or Lactobacillus iners are numerically dominant in the vaginal microenvironment of pregnant women. METHODS: The vaginal microbiomes of 157 first-trimester pregnant women were identified by classifying partial 16S gene sequences amplified from the V1 to V3 region of bacterial ribosomal 16S RNA genes...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28301138/a-secretion-amplification-role-for-salmonella-enterica-translocon-protein-sipd
#18
Anum Azam Glasgow, Han Teng Wong, Danielle Tullman-Ercek
The bacterial type III secretion system (T3SS) is an important target for enabling high-titer production of proteins of biotechnological interest as well as for synthetic biology applications that rely on protein delivery to host cells. The T3SS forms a membrane-embedded needle complex that is capped by the translocon proteins and extends into the extracellular space. The needle tip complex in Salmonella enterica consists of three translocon proteins: SipB, SipC, and SipD. It is known that knocking out sipD disrupts T3SS regulation to cause constitutive secretion of native proteins...
March 16, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28300660/mechanistic-understanding-of-the-cysteine-capping-modifications-of-antibodies-enables-selective-chemical-engineering-in-live-mammalian-cells
#19
Xiaotian Zhong, Tao He, Amar S Prashad, Wenge Wang, Justin Cohen, Darren Ferguson, Amy S Tam, Eric Sousa, Laura Lin, Lioudmila Tchistiakova, Scott Gatto, Aaron D'Antona, Yen-Tung Luan, Weijun Ma, Richard Zollner, Jing Zhou, Bo Arve, Will Somers, Ronald Kriz
Protein modifications by intricate cellular machineries often redesign the structure and function of existing proteins to impact biological networks. Disulfide bond formation between cysteine (Cys) pairs is one of the most common modifications found in extracellularly-destined proteins, key to maintaining protein structure. Unpaired surface cysteines on secreted mammalian proteins are also frequently found disulfide-bonded with free Cys or glutathione (GSH) in circulation or culture, the mechanism for which remains unknown...
March 11, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28300207/both-drosophila-matrix-metalloproteinases-have-released-and-membrane-tethered-forms-but-have-different-substrates
#20
Kimberly S LaFever, Xiaoxi Wang, Patrick Page-McCaw, Gautam Bhave, Andrea Page-McCaw
Matrix metalloproteinases (MMPs) are extracellular proteases that can cleave extracellular matrix and alter signaling pathways. They have been implicated in many disease states, but it has been difficult to understand the contribution of individual MMPs, as there are over 20 MMPs in vertebrates. The vertebrate MMPs have overlapping substrates, they exhibit genetic redundancy and compensation, and pharmacological inhibitors are non-specific. In contrast, there are only two MMP genes in Drosophila, DmMmp1 and DmMmp2, which makes Drosophila an attractive system to analyze the basis of MMP specificity...
March 16, 2017: Scientific Reports
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