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Molecular & Cellular Proteomics: MCP

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https://www.readbyqxmd.com/read/29776966/loss-of-tigar-induces-oxidative-stress-and-meiotic-defects-in-oocytes-from-obese-mice
#1
Haichao Wang, Qing Cheng, Xiaoyan Li, Feifei Hu, Longsen Han, Hao Zhang, Ling Li, Juan Ge, Xiaoyan Ying, Xuejiang Guo, Qiang Wang
Maternal obesity has been reported to impair oocyte quality in mice, however, the underlying mechanisms remain unclear. In the present study, by conducting a comparative proteomic analysis, we identified a reduced expression of TIGAR protein in ovulated oocytes from high-fat diet (HFD)-fed mice. Specific depletion of TIGAR in mouse oocytes results in the marked elevation of reactive oxygen species (ROS) levels and the failure of meiotic apparatus assembly. Importantly, forced expression of TIGAR in HFD oocytes not only attenuates ROS production, but also partly prevents spindle disorganization and chromosome misalignment during meiosis...
May 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29773674/deep-sequencing-of-complex-proteoglycans-a-novel-strategy-for-high-coverage-and-site-specific-identification-of-glycosaminoglycan-linked-peptides
#2
Joshua A Klein, Le Meng, Joseph Zaia
Proteoglycans are distributed in all animal tissues and play critical, multifaceted, physiological roles.  Expressed in a spatially- and temporally-regulated manner, these molecules regulate interactions among growth factors and cell surface receptors and play key roles in basement membranes and other extracellular matrices.  Due to the high degree of glycosylation by glycosaminoglycan (GAG), N-glycan and mucin-type O-glycan classes, the peptide sequence coverage of complex proteoglycans is revealed poorly by standard mass spectrometry-based proteomics methods...
May 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29773673/lysosomal-proteome-and-secretome-analysis-identifies-missorted-enzymes-and-their-non-degraded-substrates-in-mucolipidosis-iii-mouse-cells
#3
Giorgia Di Lorenzo, Renata Voltolini Velho, Dominic Winter, Melanie Thelen, Shiva Ahmadi, Michaela Schweizer, Raffaella De Pace, Kerstin Cornils, Timur Alexander Yorgan, Saskia Grüb, Irm Hermans-Borgmeyer, Thorsten Schinke, Sven Müller-Loennies, Thomas Braulke, Sandra Pohl
Targeting of soluble lysosomal enzymes requires mannose 6-phosphate (M6P) signals whose formation is initiated by the hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex (α2β2γ2). Upon proteolytic cleavage by site-1 protease, the α/β-subunit precursor is catalytically activated but the functions of γ-subunits (Gnptg) in M6P modification of lysosomal enzymes are unknown. To investigate this, we analyzed the Gnptg expression in mouse tissues, primary cultured cells, and in Gnptg reporter mice in vivo, and found high amounts in the brain, eye, kidney, femur, vertebra and fibroblasts...
May 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29769354/allele-specific-alterations-in-the-peptidome-underlie-the-joint-association-of-hla-a-29-02-and-endoplasmic-reticulum-aminopeptidase-2-erap2-with-birdshot-chorioretinopathy
#4
Alejandro Sanz-Bravo, Adrian Martin-Esteban, Jonas J W Kuiper, Marina García-Peydró, Eilon Barnea, Arie Admon, José A López de Castro
Virtually all patients of the rare inflammatory eye disease birdshot chorioretinopathy (BSCR) carry the HLA-A*29:02 allele. BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. To investigate the relationship between both risk factors we employed label-free quantitative mass spectrometry to characterize the effects of ERAP2 on the A*29:02-bound peptidome. An ERAP2-negative cell line was transduced with lentiviral constructs containing GFP-ERAP2 or GFP alone, and the A*29:02 peptidomes from both transduced cells were compared...
May 16, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29752379/rapid-remodeling-of-the-host-epithelial-cell-proteome-by-the-listeriolysin-o-pore-forming-toxin
#5
Julien Karim Malet, Francis Impens, Filipe Carvalho, Mélanie Anne Hamon, Pascale Cossart, David Ribet
Bacterial pathogens use various strategies to interfere with host cell functions. Among these strategies, bacteria modulate host gene transcription, thereby modifying the set of proteins synthetized by the infected cell. Bacteria can also target pre-existing host proteins and modulate their post-translational modifications or trigger their degradation. Analysis of protein levels variations in host cells during infection allows to integrate both transcriptional and post-transcriptional regulations induced by pathogens...
May 11, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29739823/butyrate-suppresses-the-proliferation-of-colorectal-cancer-cells-via-targeting-pyruvate-kinase-m2-and-metabolic-reprogramming
#6
Qingran Li, Lijuan Cao, Yang Tian, Pei Zhang, Chujie Ding, Wenjie Lu, Chenxi Jia, Chang Shao, Wenyue Liu, Dong Wang, Hui Ye, Haiping Hao
Butyrate is a short chain fatty acid present in a high concentration in the gut lumen. It has been well documented that butyrate, by serving as an energetic metabolite, promotes the proliferation of normal colonocytes while, by serving as a histone deacetylase inhibitor, epigenetically suppressing the proliferation of cancerous counterparts undergoing the Warburg effect. However, how butyrate interrupts the metabolism of colorectal cancer cells and ultimately leads to the suppression of cell proliferation remains unclear...
May 8, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29735541/multiplex-quantification-identifies-novel-exercise-regulated-myokines-cytokines-in-plasma-and-in-glycolytic-and-oxidative-skeletal-muscle
#7
Hannah Little, Stefanie Y Tan, Francesca Cali, Susana Rodriguez, Xia Lei, Andrew Wolfe, Christopher Hug, G William Wong
Exercise is known to confer major health benefits, but the underlying mechanisms are not well understood. The systemic effects of exercise on multi-organ systems are thought to be partly due to myokines/cytokines secreted by skeletal muscle. The extent to which exercise alters cytokine expression and secretion in different muscle fiber types has not been systematically examined.  Here, we assessed changes in 66 mouse cytokines in serum, and in glycolytic (plantaris) and oxidative (soleus) muscles, in response to sprint, endurance, or chronic wheel running...
May 7, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29716988/structures-of-n-glycans-of-bothrops-venoms-revealed-as-molecular-signatures-that-contribute-to-venom-phenotype-in-viperid-snakes
#8
Débora Andrade-Silva, David Ashline, Thuy Tran, Aline S Lopes, Silvia Regina Travaglia Cardoso, Marcelo S Reis, André Zelanis, Solange M T Serrano, Vernon N Reinhold
The complexity of snake venoms has long been investigated to explore a myriad of biologically active proteins and peptides that are used for immobilizing or killing prey, and are responsible for the pathological effects observed upon envenomation. Glycosylation is the main post-translational modification (PTM) of viperid venoms but currently there is little understanding of how protein glycosylation impacts the variation of venom proteomes. We have previously reported that Bothrops venom glycoproteomes contain a core of components that markedly define their composition and parallel their phylogenetic classification...
May 1, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29716987/click-chemistry-mediated-biotinylation-reveals-a-function-for-the-protease-bace1-in-modulating-the-neuronal-surface-glycoproteome
#9
Julia Herber, Jasenka Njavro, Regina Feederle, Ute Schepers, Ulrike Müller, Stefan Bräse, Stephan Müller, Stefan F Lichtenthaler
The cell surface proteome is dynamic and has fundamental roles in cell signaling. Many surface membrane proteins are proteolytically released into a cell's secretome, where they can have additional functions in cell-cell-communication. Yet, it remains challenging to determine the surface proteome and to compare it to the cell secretome, in particular under serum-containing cell culture conditions. Here, we set-up and evaluated the 'surface-spanning protein enrichment with click sugars' (SUSPECS) method for cell surface membrane glycoprotein biotinylation, enrichment and label-free quantitative mass spectrometry...
May 1, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29716986/credentialing-individual-samples-for-proteogenomic-analysis
#10
Wei Zhao, Jun Li, Rehan Akbani, Han Liang, Gordon B Mills
An integrated analysis of DNA, RNA and protein, so called proteogenomic studies, has the potential to greatly increase our understanding of both normal physiology and disease development. However, such studies are challenged by a lack of a systematic approach to credential individual samples resulting in the introduction of noise into the system that limits the ability to identify important biological signals. Indeed, a recent proteogenomic CPTAC study identified 26% of samples as unsatisfactory, resulting in a marked increase in cost and loss of information content...
May 1, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29669735/ctgf-vegfa-activated-fibroblasts-promote-tumor-migration-through-micro-environmental-modulation
#11
Wei Wu, Esther A Zaal, Celia R Berkers, Simone Lemeer, Albert J R Heck
Fibroblast activation is associated with tumour progression and implicated in metastasis, but the initial triggering signals required to kick-start this process remain largely unknown. Since small cancerous lesions share limited physical contact with neighboring fibroblasts, we reasoned the first tumour-derived signal for fibroblast activation should be secreted and diffusible. By pulsed metabolic labeling and click-chemistry based affinity enrichment, we sieved through the ductal carcinoma secretome for potential fibroblast activators...
April 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29669734/a-selective-extracellular-matrix-proteomics-approach-identifies-fibronectin-proteolysis-by-adamts16-and-its-impact-on-spheroid-morphogenesis
#12
Rahel Schnellmann, Ragna Sack, Daniel Hess, Douglas S Annis, Deane F Mosher, Suneel S Apte, Ruth Chiquet-Ehrismann
Secreted and cell-surface proteases are major mediators of extracellular matrix (ECM) turnover, but their mechanisms and regulatory impact are poorly understood. We developed a mass spectrometry approach using a cell-free ECM produced in vitro to identify fibronectin (FN) as a novel substrate of the secreted metalloprotease ADAMTS16. ADAMTS16 cleaves FN between its (I)5 and (I)6 modules, releasing the N-terminal 30 kDa heparin-binding domain essential for FN self-assembly. ADAMTS16 impairs FN fibrillogenesis as well as fibrillin-1 and tenascin-C assembly, thus inhibiting formation of a mature ECM by cultured fibroblasts...
April 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29666159/extensive-identification-and-in-depth-validation-of-importin-13-cargoes
#13
Imke Baade, Christiane Spillner, Kerstin Schmitt, Oliver Valerius, Ralph H Kehlenbach
Importin 13 is a member of the importin b family of transport receptors. Unlike most family members, importin 13 mediates both, nuclear protein import and export. To search for novel importin 13 cargoes, we used stable isotope labeling of amino acids in cell culture (SILAC) and mass spectrometry. Using stringent criteria, we identified 255 importin 13 substrates, including the known cargoes Ubc9, Mago and eIF1A, and validate many of them as transport cargoes by extensive biochemical and cell biological characterization...
April 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29666158/qc-art-a-tool-for-real-time-quality-control-assessment-of-mass-spectrometry-based-proteomics-data
#14
Bryan A Stanfill, Ernesto S Nakayasu, Lisa M Bramer, Allison M Thompson, Charles K Ansong, Therese Clauss, Marina A Gritsenko, Matthew E Monroe, Ronald J Moore, Daniel J Orton, Paul D Piehowski, Athena A Schepmoes, Richard D Smith, Bobbie-Jo Webb-Robertson, Thomas O Metz, The Environmental Determinants Of Diabetes In The Young Teddy Study Group
Liquid chromatography-mass spectrometry (LC-MS)-based proteomics studies of large sample cohorts can easily require from months to years to complete. Acquiring consistent, high-quality data in such large-scale studies is challenging because of normal variations in instrumentation performance over time, as well as artifacts introduced by the samples themselves, such as those due to collection, storage and processing. Existing quality control methods for proteomics data primarily focus on post-hoc analysis to remove low-quality data that would degrade downstream statistics; they are not designed to evaluate the data in near real-time, which would allow for interventions as soon as deviations in data quality are detected...
April 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29661852/integrated-transcriptomic-and-proteomic-analyses-suggest-the-participation-of-endogenous-protease-inhibitors-in-the-regulation-of-protease-gene-expression-in-helicoverpa-armigera
#15
Purushottam R Lomate, Veena Dewangan, Neha Mahajan, Yashwant Kumar, Abhijeet Kulkarni, Li Wang, Smita Saxsena, Vidya S Gupta, Ashok P Giri
Insects adapt to plant protease inhibitors (PIs) present in their diet by differentially regulating multiple digestive proteases. However, mechanisms regulating protease gene expression in insects are largely enigmatic. Ingestion of multi-domain recombinant Capsicum annuum protease inhibitor-7 (CanPI-7) arrests growth and development of Helicoverpa armigera (Lepidoptera: Noctuidae). Using de novo RNA sequencing and proteomic analysis, we examined the response of H. armigera larvae fed on recombinant CanPI-7 at different time intervals...
April 16, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29653959/remote-atmospheric-pressure-infrared-matrix-assisted-laser-desorption-ionization-mass-spectrometry-of-proteins
#16
Benoit Fatou, Michael Ziskind, Philippe Saudemont, Jusal Quanico, Cristian Focsa, Michel Salzet, Isabelle Fournier
Remote Infrared Matrix-Assisted Laser Desorption/Ionization (Remote IR-MALDI) system using tissue endogenous water as matrix was shown to enable in-vivo real-time mass spectrometry analysis with minimal invasiveness. Initially the system was used to detect metabolites and lipids. Here, we demonstrate its capability to detect and analyze peptides and proteins. Very interestingly, the corresponding mass spectra show ESI-like charge state distribution, opening many applications for structural elucidation to be performed in real-time by Top-Down strategy...
April 13, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29632047/identification-of-novel-response-and-predictive-biomarkers-to-hsp90-inhibitors-through-mass-spectrometry-based-proteomic-profiling-of-patient-derived-prostate-tumor-explants
#17
Elizabeth V Nguyen, Margaret M Centenera, Max Moldovan, Rajdeep Das, Swati Irani, Andrew D Vincent, Howard Chan, Lisa G Horvath, David J Lynn, Roger Daly, Lisa M Butler
Inhibition of the heat shock protein 90 (Hsp90) chaperone is a promising therapeutic strategy to target expression of the androgen receptor (AR) and other oncogenic drivers in prostate cancer cells. However, identification of clinically-relevant responses and predictive biomarkers is essential to maximize efficacy and treatment personalization. Here, we combined mass spectrometry (MS)-based proteomic analyses with a unique patient-derived explant (PDE) model that retains the complex microenvironment of primary prostate tumors...
April 9, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29632046/ranking-the-contribution-of-ankylosing-spondylitis-associated-erap1-polymorphisms-to-shaping-the-hla-b-27-peptidome
#18
Alejandro Sanz-Bravo, Carlos Alvarez-Navarro, Adrian Martín-Esteban, Eilon Barnea, Arie Admon, José A López de Castro
The Endoplasmic reticulum aminopeptidase I (ERAP1) trims peptides to their optimal size for binding to Major Histocompatibility Complex class I proteins. The natural polymorphism of this enzyme is associated with ankylosing spondylitis (AS) in epistasis with the major risk factor for this disease, HLA-B*27, suggesting a direct relationship between AS and HLA-B*27-bound peptides. Three polymorphisms that affect peptide trimming protect from AS: K528R, D575N/R725Q, and Q730E. We characterized and ranked the effects of each mutation, and their various combinations, by quantitative comparisons of the HLA-B*27 peptidomes from cells expressing distinct ERAP1 variants...
April 9, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29615496/crispr-cas9-mediated-genomic-editing-of-cluap1-ift38-reveals-a-new-role-in-actin-arrangement
#19
Tina Beyer, Sylvia Bolz, Katrin Junger, Nicola Horn, Muhammad Moniruzzaman, Yasmin Wissinger, Marius Ueffing, Karsten Boldt
CRISPR/Cas9-mediated gene editing allows manipulation of a gene of interest in its own chromosomal context. When applied to the analysis of protein interactions, and in contrast to exogenous expression of a protein, this can be studied maintaining physiological stoichiometry, topology and context. We have used CRISPR/Cas9-mediated genomic editing to investigate Cluap1/ IFT38, a component of the intraflagellar transport complex B (IFT-B). Cluap1 has been implicated in human development as well as in cancer progression...
April 3, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29615495/software-for-peak-finding-and-elemental-composition-assignment-for-glycosaminoglycan-tandem-mass-spectra
#20
John D Hogan, Joshua A Klein, Jiandong Wu, Pradeep Chopra, Geert-Jan Boons, Luis Carvalho, Cheng Lin, Joseph Zaia
Glycosaminoglycans (GAGs) covalently linked to proteoglycans (PGs) are characterized by repeating disaccharide units and variable sulfation patterns along the chain. GAG length and sulfation patterns impact disease etiology, cellular signaling, and structural support for cells. We and others have demonstrated the usefulness of tandem mass spectrometry (MS2) for assigning the structures of GAG saccharides; however, manual interpretation of tandem mass spectra is time-consuming, so computational methods must be employed...
April 3, 2018: Molecular & Cellular Proteomics: MCP
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