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https://www.readbyqxmd.com/read/27894104/proteomic-profiling-of-nci-60-extracellular-vesicles-uncovers-common-protein-cargo-and-cancer-type-specific-biomarkers
#1
Stephanie N Hurwitz, Mark A Rider, Joseph L Bundy, Xia Liu, Rakesh K Singh, David G Meckes
Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27881302/crystal-structure-of-a-full-length-human-tetraspanin-reveals-a-cholesterol-binding-pocket
#2
Brandon Zimmerman, Brendan Kelly, Brian J McMillan, Tom C M Seegar, Ron O Dror, Andrew C Kruse, Stephen C Blacklow
Tetraspanins comprise a diverse family of four-pass transmembrane proteins that play critical roles in the immune, reproductive, genitourinary, and auditory systems. Despite their pervasive roles in human physiology, little is known about the structure of tetraspanins or the molecular mechanisms underlying their various functions. Here, we report the crystal structure of human CD81, a full-length tetraspanin. The transmembrane segments of CD81 pack as two largely separated pairs of helices, capped by the large extracellular loop (EC2) at the outer membrane leaflet...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27879451/tetraspanins-and-mouse-oocyte-microvilli-related-to-fertilizing-ability
#3
Achraf Benammar, Ahmed Ziyyat, Brigitte Lefèvre, Jean-Philippe Wolf
Our electron microscopy observations demonstrate for the first time that the number of microvilli on the mice oocyte membrane decreases when meiosis progresses from prophase I to metaphase II (MII) stage, and the morphology of the microvilli also changes. Microvilli are significantly shorter and larger on the ovulated oocyte membrane than at the previous stages. Although clathrin vesicles clearly disappear during oocyte maturation, exosome-like vesicles begin to be secreted at the metaphase I stage, more strongly at the MII stage...
November 21, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27878588/the-impact-of-erdosteine-on-cisplatin-induced-ototoxicity-a-proteomics-approach
#4
Sofia Waissbluth, Delphine Garnier, Olubunmi V Akinpelu, Pezhman Salehi, Sam J Daniel
Cisplatin is a commonly used chemotherapeutic agent and causes serious side effects, including progressive and irreversible hearing loss. No treatment is currently available for cisplatin-induced ototoxicity. We have previously demonstrated that erdosteine, a potent antioxidant, partially protected the cochlea against cisplatin toxicity in vivo. The aims of this study were to (1) evaluate the protein profiles of the cochlea following cisplatin administration and (2) evaluate the impact of erdosteine on the protein profile using a proteomics-based approach...
November 23, 2016: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/27860532/hepatitis-c-virus-e2-protein-induces-upregulation-of-il-8-pathways-and-production-of-heat-shock-proteins-in-human-thyroid-cells
#5
Sara Salehi Hammerstad, Mihaela Stefan, Jason Blackard, Randall P Owen, Hanna J Lee, Erlinda Concepcion, Zhengzi Yi, Weijia Zhang, Yaron Tomer
CONTEXT: Thyroiditis is one of the most common extra hepatic manifestations of hepatitis C virus infection. By binding to surface cell receptor CD81, hepatitis C envelop glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals...
November 18, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27856179/exosomal-proteins-as-prognostic-biomarkers-in-non-small-cell-lung-cancer
#6
B Sandfeld-Paulsen, N Aggerholm-Pedersen, R Bæk, K R Jakobsen, P Meldgaard, B H Folkersen, T R Rasmussen, K Varming, M M Jørgensen, B S Sorensen
BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes...
October 21, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27843938/wnt-%C3%AE-catenin-signaling-promotes-the-maturation-of-mast-cells
#7
Tomoko Yamaguchi, Misae Nishijima, Katsuhisa Tashiro, Kenji Kawabata
Mast cells play an important role in the pathogenesis of allergic diseases. Immature mast cells migrate into peripheral tissues from the bone marrow and undergo complete maturation. Interestingly, mast cells have characteristics similar to hematopoietic stem cells (HSCs), such as self-renewal and c-kit expression. In HSCs, Wnt signaling is involved in their maintenance and differentiation. On the other hand, the relation between Wnt signaling and mast cell differentiation is poorly understood. To study whether Wnt signals play a role in the maturation of mast cells, we studied the effect of Wnt proteins on mast cell maturation of bone marrow-derived mast cells (BMMCs)...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27834208/expanding-the-host-range-of-hepatitis-c-virus-through-viral-adaptation
#8
Markus von Schaewen, Marcus Dorner, Kathrin Hueging, Lander Foquet, Sherif Gerges, Gabriela Hrebikova, Brigitte Heller, Julia Bitzegeio, Juliane Doerrbecker, Joshua A Horwitz, Gisa Gerold, Sebastian Suerbaum, Charles M Rice, Philip Meuleman, Thomas Pietschmann, Alexander Ploss
: Hepatitis C virus (HCV) species tropism is incompletely understood. We have previously shown that at the level of entry, human CD81 and occludin (OCLN) comprise the minimal set of human factors needed for viral uptake into murine cells. As an alternative approach to genetic humanization, species barriers can be overcome by adapting HCV to use the murine orthologues of these entry factors. We previously generated a murine tropic HCV (mtHCV or Jc1/mCD81) strain harboring three mutations within the viral envelope proteins that allowed productive entry into mouse cell lines...
November 8, 2016: MBio
https://www.readbyqxmd.com/read/27818281/gpr56-adgrg1-activation-promotes-melanoma-cell-migration-via-ntf-dissociation-and-ctf-mediated-g%C3%AE-12-13-rhoa-signaling
#9
Nien-Yi Chiang, Yen-Ming Peng, Horng-Heng Juang, Tse-Ching Chen, Hsiao-Lin Pan, Gin-Wen Chang, Hsi-Hsien Lin
GPR56/ADGRG1 is a versatile adhesion G protein-coupled receptor with diverse biological functions. GPR56 expression is variably detected in human melanoma cell lines and correlates inversely with the metastatic potential of melanoma lesions. GPR56 associates with the tetraspanins CD9 and CD81 on melanoma cell surface. GPR56 activation by immobilized CG4 mAb facilitates NTF dissociation in a CD9/CD81-dependent manner specifically inducing IL-6 production, which promotes cell migration and invasion. Interestingly, expression of GPR56-CTF alone recapitulates the antibody-induced receptor function, implicating a major role for the CTF in GPR56 activation and signaling...
November 3, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27791120/structural-flexibility-at-a-major-conserved-antibody-target-on-hepatitis-c-virus-e2-antigen
#10
Leopold Kong, David E Lee, Rameshwar U Kadam, Tong Liu, Erick Giang, Travis Nieusma, Fernando Garces, Netanel Tzarum, Virgil L Woods, Andrew B Ward, Sheng Li, Ian A Wilson, Mansun Law
Hepatitis C virus (HCV) is a major cause of liver disease, affecting over 2% of the world's population. The HCV envelope glycoproteins E1 and E2 mediate viral entry, with E2 being the main target of neutralizing antibody responses. Structural investigations of E2 have produced templates for vaccine design, including the conserved CD81 receptor-binding site (CD81bs) that is a key target of broadly neutralizing antibodies (bNAbs). Unfortunately, immunization with recombinant E2 and E1E2 rarely elicits sufficient levels of bNAbs for protection...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27766647/the-effect-of-microenvironmental-factors-on-the-development-of-myeloma-cells
#11
Ágnes Márk, Gergely Varga, Botond Timár, Csilla Kriston, Orsolya Szabó, Linda Deák, András Matolcsy, Gábor Barna
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of monoclonal plasma cells (PCs) in the bone marrow and other tissues. Although there are several new therapies, MM remains fatal. The interaction between MM cells and the bone marrow microenvironment promotes drug resistance and cancer cells survival. In our present work, we compared the antigen expression pattern of normal and pathological PCs and investigated the possible connections between various surface receptors, adhesion molecules, and recurrent genetic aberrations...
October 21, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27725852/microrna-155-in-exosomes-secreted-from-helicobacter-pylori-infection-macrophages-immunomodulates-inflammatory-response
#12
Jianjun Wang, Zhiyong Deng, Zeyou Wang, Jianhong Wu, Tao Gu, Yibiao Jiang, Guangxin Li
Exosomes containing microRNA-155 act as molecule carriers during immune cell-cell communication and play an important role in the inflammatory response of H. pylori infection macrophages. Previous reports have found that miR-155 was over-expressed in H. pylori infection macrophages, but the significance of which is still unknown. In this study, we analyzed the impact of miR-155 loaded in exosomes derived from macrophages to the inflammatory response of H. pylori infection macrophages and possible mechanisms...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27693511/infection-of-hepatocytes-with-hcv-increases-cell-surface-levels-of-heparan-sulfate-proteoglycans-uptake-of-cholesterol-and-lipoprotein-and-virus-entry-by-up-regulating-smad6-and-smad7
#13
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6, and another inhibitory SMAD (SMAD7), promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with JFH1 HCVcc; we measured HCV binding, intracellular levels of HCV RNA, and expression of target genes...
September 30, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27679865/characterization-of-tetraspanin-protein-cd81-in-mouse-spermatozoa-and-bovine-gametes
#14
Jana Jankovicova, Michaela Frolikova, Natasa Sebkova, Michal Simon, Petra Cupperova, Denisa Lipcseyova, Katarina Michalkova, Lubica Horovska, Radislav Sedlacek, Pavel Stopka, Jana Antalikova, Katerina Dvorakova-Hortova
Sperm-egg interaction and fusion represents a key moment of fertilization and it would not happen in mammals without the interaction of the tetraspanin superfamily members including protein CD81. A detailed immunohistochemical localization of CD81 was monitored on bovine oocytes of different maturation stages, as well as during early embryogenesis. There was also a CD81characterization on bovine and mouse sperm carried out. On bovine eggs, CD81 was detected on the plasma membrane of the germinal vesicle, metaphase I and metaphase II oocytes...
September 27, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27678340/production-of-infectious-hcv-genotype-1b-virus-in-cell-culture-using-a-novel-set-of-adaptive-mutations
#15
Ken-Ichi Mori, Akihiro Matsumoto, Noboru Maki, Yuki Ichikawa, Eiji Tanaka, Shintaro Yagi
BACKGROUND: Despite the high prevalence of genotype 1b hepatitis C virus (HCV) among patients, a cell culture system that permits entire viral life cycle of genotype 1b isolates is limited. To develop a cell-cultured hepatitis C virus (HCVcc) of genotype 1b, the proper combination of HCV genomic variants and host cells is essential. HCV genomes isolated from patients with distinctive symptoms may provide the variants required to establish an HCVcc of genotype 1b. RESULTS: We first established subgenomic replicons in Huh7 cells using HCV cDNAs isolated from two patients: one with fulminant hepatitis after liver transplantation (TPF1) and another with acute hepatitis and moderate symptoms (sAH)...
September 27, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27641977/preferential-association-of-hepatitis-c-virus-with-cd19-b-cells-is-mediated-by-complement-system
#16
Richard Y Wang, Patricia Bare, Valeria De Giorgi, Kentaro Matsuura, Kazi Abdus Salam, Teresa Grandinetti, Cathy Schechterly, Harvey J Alter
: Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells from chronically infected patients is mainly associated with cluster of differentiation 19-positive (CD19(+) ) B cells. To further elucidate this preferential association of HCV with B cells, we used in vitro cultured virus and uninfected peripheral blood mononuclear cells from healthy blood donors to investigate the necessary serum components that activate the binding of HCV to B cells...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27640641/size-exclusion-chromatography-based-isolation-minimally-alters-extracellular-vesicles-characteristics-compared-to-precipitating-agents
#17
Ana Gámez-Valero, Marta Monguió-Tortajada, Laura Carreras-Planella, Marcel la Franquesa, Katrin Beyer, Francesc E Borràs
Extracellular vesicles (EVs) have become an attractive field among the scientific community. Yet, a major challenge is to define a consensus method for EVs isolation. Ultracentrifugation has been the most widely used methodology but rapid methods, including Size Exclusion Chromatography (SEC) and/or precipitating agents such as Polyethylene glycol (PEG) or PRotein Organic Solvent PRecipitation (PROSPR) have emerged. To evaluate the impact of these different methods on the resulting EV preparations, plasma EVs were isolated using SEC, PEG and PROSPR, and their total protein content, NTA and Cryo-electron microscopy profiles, and EV-markers were compared...
September 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27630236/a-library-of-infectious-hepatitis-c-viruses-with-engineered-mutations-in-the-e2-gene-reveals-growth-adaptive-mutations-that-modulate-interactions-with-scavenger-receptor-class-b-type-i
#18
Adam Zuiani, Kevin Chen, Megan C Schwarz, James P White, Vincent C Luca, Daved H Fremont, David Wang, Matthew J Evans, Michael S Diamond
: While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27592404/hepatoprotective-effect-of-exosomes-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-against-hepatic-ischemia-reperfusion-injury-in-rats
#19
Kate Nong, Weiwei Wang, Xin Niu, Bin Hu, Chenchao Ma, Yueqing Bai, Bo Wu, Yang Wang, Kaixing Ai
BACKGROUND: This study aimed to evaluate the effect of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury. METHODS: Exosomes were isolated and concentrated from conditioned medium using ultracentrifugation and ultrafiltration. hiPSC-MSCs-Exo were injected systemically via the inferior vena cava in a rat model of 70% warm hepatic I/R injury, and the therapeutic effect was evaluated...
August 31, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27574733/combination-of-neutralizing-monoclonal-antibodies-against-hepatitis-c-virus-e2-protein-effectively-blocks-virus-infection
#20
Mihika Bose, Ranajoy Mullick, Soma Das, Saumitra Das, Anjali A Karande
Hepatitis C virus (HCV) represents a major global health threat. The envelope glycoproteins, E1-E2 of HCV play an important role in infection by binding to hepatocyte surface receptors leading to viral entry. Several regions on the E1-E2 are conserved for maintaining structural stability, despite the high mutation rate of HCV. Identification of antigenic determinants in these domains would aid in the development of anti-virals. The present study was aimed to delineate neutralizing epitopes by generating monoclonal antibodies (mAbs) to envelope proteins that can block virus binding and entry...
September 15, 2016: Virus Research
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