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human proteome

Mafalda Santos, Patricia M Pereira, A Sofia Varanda, Joana Carvalho, Mafalda Azevedo, Denisa D Mateus, Nuno Mendes, Patricia Oliveira, Fábio Trindade, Marta Teixeira Pinto, Renata Bordeira-Carriço, Fátima Carneiro, Rui Vitorino, Carla Oliveira, Manuel A S Santos
Deregulation of tRNAs, aminoacyl-tRNA synthetases and tRNA modifying enzymes are common in cancer, raising the hypothesis that protein synthesis efficiency and accuracy (mistranslation) are compromised in tumors. We show here that human colon tumors and xenograft tumors produced in mice by two epithelial cancer cell lines mistranslate 2- to 4-fold more frequently than normal tissue. To clarify if protein mistranslation plays a role in tumor biology, we expressed mutant Ser-tRNAs that misincorporate Ser-at-Ala (frequent error) and Ser-at-Leu (infrequent error) in NIH3T3 cells and investigated how they responded to the proteome instability generated by the amino acid misincorporations...
March 20, 2018: RNA Biology
Nuray Erin, Nur Ogan, Azmi Yerlikaya
PURPOSE: Metastatic breast cancer is resistant to many conventional treatments and novel therapeutic targets are needed. We previously isolated subsets of 4T1 murine breast cancer cells which metastasized to liver (4TLM), brain (4TBM), and heart (4THM). Among these cells, 4TLM is the most aggressive one, demonstrating mesenchymal phenotype. Here we compared secreted proteins from 4TLM, 4TBM, and 4THM cells and compared with that of hardly metastatic 67NR cells to detect differentially secreted factors involved in organ-specific metastasis...
March 20, 2018: Breast Cancer Research and Treatment
Kai Li, Yue Zhang, Yuwei Zhang, Wenqing Jiang, Junhui Shen, Song Xu, Daozhang Cai, Jie Shen, Bin Huang, Mangmang Li, Qiancheng Song, Yu Jiang, Anling Liu, Xiaochun Bai
OBJECTIVES: To investigate the role of tyrosine kinase Fyn in the development of osteoarthritis (OA) and the underlying mechanisms, and to define whether targeting Fyn could prevent OA in mice. METHODS: Cartilage samples from normal and aged mice were analysed with proteome-wide screening. Fyn expression was examined with immunofluorescence in human and age-dependent or experimental mouse OA cartilage samples. Experimental OA in Fyn-knockout mice was induced by destabilisation of the medial meniscus...
March 19, 2018: Annals of the Rheumatic Diseases
Loredana Campo, Eun-Kyoung Breuer
Studies have shown that transforming acidic coiled-coil protein 3 (TACC3), a key component of centrosome-microtubule dynamic networks, is significantly associated with various types of human cancer. We have recently reported that high levels of TACC3 are found in breast cancer, lead to the accumulation of spontaneous DNA damage due to defective DNA damage response signaling, and confer cellular sensitivity to radiation and poly(ADP-ribose) polymerase (PARP) inhibitors. Although our study suggests a potential role of TACC3 as a biomarker in breast cancer detection and prediction of therapy outcome, its role as a therapeutic target in breast cancer is not well studied...
March 16, 2018: Biochemical and Biophysical Research Communications
Alexander L Greninger, Giselle M Knudsen, Pavitra Roychoudhury, Derek J Hanson, Ruth Hall Sedlak, Hong Xie, Jon Guan, Thuy Nguyen, Vikas Peddu, Michael Boeckh, Meei-Li Huang, Linda Cook, Daniel P Depledge, Danielle M Zerr, David M Koelle, Soren Gantt, Tetsushi Yoshikawa, Mary Caserta, Joshua A Hill, Keith R Jerome
BACKGROUND: Human herpesvirus-6A and -6B (HHV-6) are betaherpesviruses that reach > 90% seroprevalence in the adult population. Unique among human herpesviruses, HHV-6 can integrate into the subtelomeric regions of human chromosomes; when this occurs in germ line cells it causes a condition called inherited chromosomally integrated HHV-6 (iciHHV-6). Only two complete genomes are available for replicating HHV-6B, leading to numerous conflicting annotations and little known about the global genomic diversity of this ubiquitous virus...
March 20, 2018: BMC Genomics
Yiling Li, Bin He, Jiejun Gao, Qian S Liu, Runzeng Liu, Guangbo Qu, Jianbo Shi, Ligang Hu, Guibin Jiang
The neurotoxic effects of methylmercury (MeHg) have been intensively studied. However, the molecular mechanisms responsible for the neurotoxicity of MeHg are not fully understood. To decipher these mechanisms, proteomic and high-throughput mRNA sequencing (RNA-seq) technique were utilized, comprehensively evaluating the cellular responses of human neuroblastoma SK-N-SH cells to MeHg exposure. Proteomic results revealed that MeHg exposure interfered with RNA splicing via splicesome, along with the known molecular mechanisms of mercury-related neurotoxicity (e...
March 16, 2018: Environmental Pollution
Phillip Munson, Ying-Wai Lam, Julie Dragon, Maximilian MacPherson, Arti Shukla
Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma...
March 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Peter D Koch, Howard R Miller, Gary Yu, John A Tallarico, Peter K Sorger, Yuan Wang, Yan Feng, Jason R Thomas, Nathan T Ross, Timothy Mitchison
We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways...
March 19, 2018: ACS Chemical Biology
Lisa A Sawicki, Leila H Choe, Katherine L Wiley, Kelvin H Lee, April M Kloxin
Cells interact with and remodel their microenvironment, degrading large extracellular matrix (ECM) proteins (e.g., fibronectin, collagens) and secreting new ECM proteins and small soluble factors (e.g., growth factors, cytokines). Synthetic mimics of the ECM have been developed as controlled cell culture platforms for use in both fundamental and applied studies. However, how cells broadly remodel these initially well-defined matrices remains poorly understood and difficult to probe. In this work, we have established methods for widely examining both large and small proteins that are secreted by cells within synthetic matrices...
March 12, 2018: ACS Biomaterials Science & Engineering
Stephanie Makhoul, Elena Walter, Oliver Pagel, Ulrich Walter, Albert Sickmann, Stepan Gambaryan, Albert Smolenski, René P Zahedi, Kerstin Jurk
Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome...
March 14, 2018: Nitric Oxide: Biology and Chemistry
Xabier Osteikoetxea, Márton Benke, Marta Rodriguez, Krisztina Pálóczi, Barbara W Sódar, Zsuzsanna Szvicsek, Katalin Szabó-Taylor, Krisztina V Vukman, Ágnes Kittel, Zoltán Wiener, Károly Vékey, László Harsányi, Ákos Szűcs, Lilla Turiák, Edit I Buzás
AIMS: The prognosis of patients with pancreatic cancer has remained virtually unchanged with a high mortality rate compared to other types of cancers. An earlier detection would provide a time window of opportunity for treatment and prevention of deaths. In the present study we investigated extracellular vesicle (EV)-associated potential biomarkers for pancreatic cancer by directly assessing EV size-based subpopulations in pancreatic juice samples of patients with chronic pancreatitis or pancreatic cancer...
March 14, 2018: Biochemical and Biophysical Research Communications
Kai Yu, Paula Andruschak, Han Hung Yeh, Dana Grecov, Jayachandran N Kizhakkedathu
The information regarding the nature of protein corona (and its changes) and cell binding on biomaterial surface under dynamic conditions is critical to dissect the mechanism of surface-induced thrombosis. In this manuscript, we investigated the nature of protein corona and blood cell binding in heparinized recalcified human plasma, platelet rich plasma and whole blood on three highly hydrophilic antifouling polymer brushes, (poly(N, N-dimethylacrylamide) (PDMA), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) using an in vitro blood loop model at comparable arterial and venous flow, and static conditions...
March 8, 2018: Biomaterials
Konrad Sachse, Kh Shamsur Rahman, Christiane Schnee, Elke Müller, Madlen Peisker, Thomas Schumacher, Evelyn Schubert, Anke Ruettger, Bernhard Kaltenboeck, Ralf Ehricht
Serological analysis of Chlamydia (C.) spp. infections is still mainly based on micro-immunofluorescence and ELISA. To overcome the limitations of conventional serology, we have designed a novel microarray carrying 52 synthetic peptides representing B-cell epitopes from immunodominant proteins of all 11 chlamydial species. The new assay has been validated using monospecific mouse hyperimmune sera. Subsequently, serum samples from cattle, sheep and humans with a known history of chlamydial infection were examined...
March 16, 2018: Scientific Reports
Theresa Stolle, Freya Grondinger, Andreas Dunkel, Thomas Hofmann
Recently, studies on human salt taste sensitivity demonstrated that sodium chloride (NaCl) sensitive and non-sensitive subjects differed in their salivary proteome and, in particular, in endopeptidase activity. In order to investigate individual's NaCl sensitivity and the role of endoprotease activity in salt taste perception, 20 panellists were classified according to NaCl sensitivity and saliva samples collected. A targeted protein quantitation by means of selected-reaction-monitoring (SRM) mass spectrometry and stable-isotope incorporation revealed the joint abundance of lysozyme C and lipocalin-1 to be indicative for non-sensitive subjects...
July 15, 2018: Food Chemistry
Ana Carla Peixoto Guissoni, Célia Maria Almeida Soares, Kareem R Badr, Fabiola Sousa Ficcadori, Ana Flávia Alves Parente, Juliana Alves Parente, Lilian Cristina Baeza, Menira Souza, Divina das Dores de Paula Cardoso
Human Adenoviruses (HAdVs) are etiological agents of different syndromes such as gastroenteritis, cystitis, ocular, and respiratory diseases, and infection by these viruses may cause alterations in cellular homeostasis. The objective of the study was the proteomic analysis of A-549 cells infected with HAdV-40 using LC-MS. At 30 h of infection, the quantitative analysis revealed 336 differentially expressed proteins. From them, 206 were induced (up-regulated) and 130 were suppressed (down-regulated). The majority of up-regulated proteins were related to energy, cellular organization, stress response, and apoptosis pathways...
March 15, 2018: Virus Genes
Harriet C Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Webb, Luk J R Rombauts, Beverley J Vollenhoven, Lois A Salamonsen, Tracey A Edgell
The regenerative, proliferative phase of a woman's menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined. We hypothesized that alterations in the secreted proteome of the endometrium of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration...
March 13, 2018: Biology of Reproduction
Arantza Infante, Clara I Rodríguez
Aging is a complex biological process, which involves multiple mechanisms with different levels of regulation. Senescent cells are known to secrete senescence-associated proteins, which exert negative influences on surrounding cells. Mesenchymal stem cells (MSCs), the common progenitors for bone, cartilage and adipose tissue (which are especially affected tissues in aging), are known to secrete a broad spectrum of biologically active proteins with both paracrine and autocrine functions in many biological processes...
March 15, 2018: Scientific Reports
Alina Fedoseienko, Melinde Wijers, Justina C Wolters, Daphne Dekker, Marieke Smit, Nicolette Huijkman, Niels Kloosterhuis, Helene Klug, Aloys Schepers, Ko Willems van Dijk, Johannes H Levels, Daniel D Billadeau, Marten H Hofker, Jan van Deursen, Marit Westerterp, Ezra Burstein, Jan Albert Kuivenhoven, Bart van de Sluis
<u>Rationale:</u> <u>CO</u> pper<u>M</u>etabolism<u>M</u>URR1 Domain-containing (COMMD) proteins are a part of the COMMD-CCDC22-CCDC93 (CCC) complexes facilitating endosomal trafficking of cell surface receptors. Hepatic COMMD1 inactivation decreases CCDC22 and CCDC93 protein levels, impairs the recycling of the low-density lipoprotein receptor (LDLR), and increases plasma LDL cholesterol levels in mice. However, whether any of the other COMMD members function similarly as COMMD1, and whether perturbation in the CCC complex promotes atherogenesis remain unclear...
March 15, 2018: Circulation Research
He Wang, Jianjia Li, Xiaoyi Zhang, Tingting Ning, Dandan Ma, Yihong Ge, Shuaimei Xu, Yilin Hao, Buling Wu
To seek a potential target for periodontal tissue regeneration, this study aimed to explore the role of Integrin alpha 5 (ITGA5) in human periodontal ligament stem cells (PDLSCs). Transwell assay, Cell Counting Kit 8 (CCK8) assay, cell cycle assay, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot were used to investigate the effects of ITGA5 on PDLSC migration, proliferation and osteogenic differentiation. The in vivo effect was investigated by nude mice subcutaneous transplantation with cell and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) complex...
March 12, 2018: Journal of Proteomics
Jaime Ibarrola, Rafael Sádaba, Amaia Garcia-Peña, Vanessa Arrieta, Ernesto Martinez-Martinez, Virginia Alvarez, Amaya Fernández-Celis, Alicia Gainza, Enrique Santamaría, Joaquin Fernández-Irigoyen, Victoria Cachofeiro, Renaud Fay, Patrick Rossignol, Natalia López-Andrés
AIMS: Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in cardiac inflammation and fibrosis, could regulate oxidative stress, although the mechanisms have not been elucidated. We herein investigated the changes in oxidative stress-related mediators induced by Gal-3 in human cardiac fibroblasts and in pathological animal and human models of cardiac diseases. RESULTS: Using quantitative proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated fumarate hydratase (FH) in human cardiac fibroblasts...
May 1, 2018: International Journal of Cardiology
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