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Allan r brasier

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https://www.readbyqxmd.com/read/28874504/proteome-analysis-of-hypoxic-glioblastoma-cells-reveals-sequential-metabolic-adaptation-nbsp-of-one-carbon-metabolic-pathways
#1
Kangling Zhang, Pei Xu, James L Sowers, Daniel F Machuca, Barsam Mirfattah, Jason Herring, Hui Tang, Yan Chen, Bing Tian, Allan R Brasier, Lawrence C Sowers
Rapidly proliferating tumors are exposed to a hypoxic microenvironment due to their density, high metabolic consumption, and interruptions in blood flow due to immature angiogenesis. Cellular responses to hypoxia promote highly malignant and metastatic behavior, as well as a chemotherapy-resistant state. In order to better understand the complex relationships between hypoxic adaptations and cancer progression, we studied the dynamic proteome responses of glioblastoma cells exposed to hypoxia via an innovative approach: quantification of newly synthesized proteins using heavy stable-isotope arginine labeling combined with accurate assessment of cell replication by quantification of the light/heavy arginine ratio of peptides in histone H4...
September 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28819550/effects-of-storage-temperature-on-airway-exosome-integrity-for-diagnostic-and-functional-analyses
#2
Rosario Maroto, Yingxin Zhao, Mohammad Jamaluddin, Vsevolod L Popov, Hongwang Wang, Madumali Kalubowilage, Yueqing Zhang, Jonathan Luisi, Hong Sun, Christopher T Culbertson, Stefan H Bossmann, Massoud Motamedi, Allan R Brasier
Background: Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim: We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods: Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or -80°C...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28818856/deletion-of-nf-%C3%AE%C2%BAb-rela-in-angiotensin-ii-sensitive-mesenchymal-cells-blocks-aortic-vascular-inflammation-and-abdominal-aortic-aneurysm-formation
#3
Talha Ijaz, Hong Sun, Irina V Pinchuk, Dianna M Milewicz, Ronald G Tilton, Allan R Brasier
OBJECTIVE: Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28798252/pollen-induced-oxidative-dna-damage-response-regulates-mirnas-controlling-allergic-inflammation
#4
Leopoldo Aguilera-Aguirre, Wenjing Hao, Lang Pan, Xiaoxue Li, Alfredo Saavedra-Molina, Attila Bacsi, Zsolt Radak, Sanjiv Sur, Allan R Brasier, Xueqing Ba, Istvan Boldogh
A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28726418/quantitative-assessment-of-the-effects-of-trypsin-digestion-methods-on-affinity-purification-mass-spectrometry-based-protein-protein-interaction-analysis
#5
Yueqing Zhang, Hong Sun, Jing Zhang, Allan R Brasier, Yingxin Zhao
Affinity purification-mass spectrometry (AP-MS) has become the method of choice for discovering protein-protein interactions (PPIs) under native conditions. The success of AP-MS depends on the efficiency of trypsin digestion and the recovery of the tryptic peptides for MS analysis. Several different protocols have been used for trypsin digestion of protein complexes in AP-MS studies, but no systematic studies have been conducted on the impact of trypsin digestion conditions on the identification of PPIs. Here, we used NFκB/RelA and Bromodomain-containing protein 4 (BRD4) as baits and test five distinct trypsin digestion methods (two using "on-beads," three using "elution-digestion" protocols)...
July 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28714690/selective-affinity-enrichment-of-nitrotyrosine-containing-peptides-for-quantitative-analysis-in-complex-samples
#6
Yingxin Zhao, Yueqing Zhang, Hong Sun, Rosario Maroto, Allan R Brasier
Protein tyrosine nitration by oxidative and nitrate stress is important in the pathogenesis of many inflammatory or aging-related diseases. Mass spectrometry analysis of protein nitrotyrosine is very challenging because the non-nitrated peptides suppress the signals of the low-abundance nitrotyrosine (NT) peptides. No validated methods for enrichment of NT-peptides are currently available. Here we report an immunoaffinity enrichment of NT-peptides for proteomics analysis. The effectiveness of this approach was evaluated using nitrated protein standards and whole-cell lysates in vitro...
July 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28666081/major-histocompatibility-complex-class-ii-alleles-influence-induction-of-pathogenic-antiphospholipid-antibodies-in-a-mouse-model-of-thrombosis
#7
Elizabeth Papalardo, Zurina Romay-Penabad, Rohan Willis, Premkumar Christadoss, Ana Laura Carrera-Marin, Elba Reyes-Maldonado, Rajani Rudrangi, Silvana Alfieri-Papalardo, Ethel Garcia-Latorre, Miri Blank, Silvia Pierangeli, Allan R Brasier, Emilio B Gonzalez
OBJECTIVE: Both environmental and genetic factors are important in the development of antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). Currently, the only available data on predisposing genetic factors have been obtained from epidemiologic studies, without mechanistic evidence. Therefore, we studied the influence of major histocompatibility complex (MHC) class II alleles on the production of aPL in a mouse model of APS. METHODS: Three groups of mice, MHC class II-deficient (MHCII(-/-) ) mice, MHCII(-/-) mice transgenic for human HLA-DQ6 (DQ6), DQ8, or DR4 alleles, and the corresponding wild-type (WT) mouse strains were immunized; half were immunized with human β2 -glycoprotein I (β2 GPI), and the other half were immunized with control ovalbumin (OVA) protein...
June 30, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28583369/innate-mechanism-of-pollen-and-cat-dander-induced-oxidative-stress-and-dna-damage-in-airways
#8
Koa Hosoki, David Redding, Toshiko Itazawa, Anirban Chakraborty, Nisha Tapryal, Sun Qian, Huibin Qi, Leopoldo Aguilera-Aguirre, Allan R Brasier, Sreenivas Phani Veeranki, Tapas K Hazra, Istvan Boldogh, Sanjiv Sur
Specific allergenic extracts induce TLR4-dependent oxidative stress and DNA damage.
June 2, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28581456/epigenetic-silencing-of-irf1-dysregulates-type-iii-interferon-responses-to-respiratory-virus-infection-in-epithelial-to-mesenchymal-transition
#9
Jun Yang, Bing Tian, Hong Sun, Roberto P Garofalo, Allan R Brasier
Chronic oxidative injury produced by airway disease triggers a transforming growth factor-β (TGF-β)-mediated epigenetic reprogramming known as the epithelial-mesenchymal transition (EMT). We observe that EMT silences protective mucosal interferon (IFN)-I and III production associated with enhanced rhinovirus (RV) and respiratory syncytial virus (RSV) replication. Mesenchymal transitioned cells are defective in inducible interferon regulatory factor 1 (IRF1) expression by occluding RelA and IRF3 access to the promoter...
June 5, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28258195/systematic-analysis-of-cell-type-differences-in-the-epithelial-secretome-reveals-insights-into-the-pathogenesis-of-respiratory-syncytial-virus-induced-lower-respiratory-tract-infections
#10
Yingxin Zhao, Mohammad Jamaluddin, Yueqing Zhang, Hong Sun, Teodora Ivanciuc, Roberto P Garofalo, Allan R Brasier
Lower respiratory tract infections from respiratory syncytial virus (RSV) are due, in part, to secreted signals from lower airway cells that modify the immune response and trigger airway remodeling. To understand this process, we applied an unbiased quantitative proteomics analysis of the RSV-induced epithelial secretory response in cells representative of the trachea versus small airway bronchiolar cells. A workflow was established using telomerase-immortalized human epithelial cells that revealed highly reproducible cell type-specific differences in secreted proteins and nanoparticles (exosomes)...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28195723/drug-discovery-targeting-bromodomain-containing-protein-4
#11
REVIEW
Zhiqing Liu, Pingyuan Wang, Haiying Chen, Eric A Wold, Bing Tian, Allan R Brasier, Jia Zhou
BRD4, the most extensively studied member of the BET family, is an epigenetic regulator that localizes to DNA via binding to acetylated histones and controls the expression of therapeutically important gene regulatory networks through the recruitment of transcription factors to form mediator complexes, phosphorylating RNA polymerase II, and by its intrinsic histone acetyltransferase activity. Disrupting the protein-protein interactions between BRD4 and acetyl-lysine has been shown to effectively block cell proliferation in cancer, cytokine production in acute inflammation, and so forth...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28182006/coordinate-activities-of-brd4-and-cdk9-in-the-transcriptional-elongation-complex-are-required-for-tgf%C3%AE-induced-nox4-expression-and-myofibroblast-transdifferentiation
#12
Talha Ijaz, Mohammad Jamaluddin, Yingxin Zhao, Yueqing Zhang, Jayson Jay, Celeste C Finnerty, David N Herndon, Ronald G Tilton, Allan R Brasier
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28145773/reply-protease-plays-a-role-in-ragweed-pollen-induced-neutrophil-recruitment-and-epithelial-barrier-disruption
#13
Koa Hosoki, Allan R Brasier, Alexander Kurosky, Istvan Boldogh, Sanjiv Sur
No abstract text is available yet for this article.
February 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28077651/brd4-couples-nf-%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#14
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to respiratory syncytial virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NF-κB/RelA. BRD4 is functionally required for expression of the NF-κB-dependent inflammatory gene regulatory network (GRN), including the IFN response factor 1 (IRF1) and IRF7, which mediate a cross talk pathway for RIG-I upregulation...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27975232/qualification-and-verification-of-protein-biomarker-candidates
#15
REVIEW
Yingxin Zhao, Allan R Brasier
The importance of biomarkers has long been recognized by the public, scientific community, and industry. Yet despite extensive efforts and funding investments in biomarker discovery, only 109 protein biomarkers in plasma or serum were approved by the US Food and Drug Administration throughout 2008 (Anderson NL. Clin Chem 56:177-185, 2010), and even fewer protein biomarkers are currently used routinely in the clinic. In recent years, the introduction of new protein biomarkers approved by the US Food and Drug Administration has fallen to an average of 1...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27975229/introduction-to-clinical-proteomics
#16
REVIEW
John E Wiktorowicz, Allan R Brasier
Within the context of this section, biomarkers are defined as a panel of proteins and peptides that are predictive of the risk for developing a pathological condition. It is important to note here that the use of the descriptor 'panel' is purposeful in that single "biomarkers" are rarely sufficient to permit accurate prediction of a pathological condition. More specifically, the primary application of a biomarker panel is that it serves as a molecular indicator of the severity of a disease or its early response to treatment...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27911568/nf-%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#17
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multicellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll-like receptor (TLR) 3 pathway by extracellular polyinosinic:polycytidylic acid (poly[I:C]) induces innate signaling through the NF-κB transcription factor in normal human small airway epithelial cells, prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition, and activation of a fibrotic program...
April 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27793799/brd4-mediates-nf-%C3%AE%C2%BAb-dependent-epithelial-mesenchymal-transition-and-pulmonary-fibrosis-via-transcriptional-elongation
#18
Bing Tian, Yingxin Zhao, Hong Sun, Yueqing Zhang, Jun Yang, Allan R Brasier
Chronic epithelial injury triggers a TGF-β-mediated cellular transition from normal epithelium into a mesenchymal-like state that produces subepithelial fibrosis and airway remodeling. Here we examined how TGF-β induces the mesenchymal cell state and determined its mechanism. We observed that TGF-β stimulation activates an inflammatory gene program controlled by the NF-κB/RelA signaling pathway. In the mesenchymal state, NF-κB-dependent immediate-early genes accumulate euchromatin marks and processive RNA polymerase...
December 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27756845/oxidized-guanine-base-lesions-function-in-8-oxoguanine-dna-glycosylase-1-mediated-epigenetic-regulation-of-nuclear-factor-%C3%AE%C2%BAb-driven-gene-expression
#19
Lang Pan, Bing Zhu, Wenjing Hao, Xianlu Zeng, Spiros A Vlahopoulos, Tapas K Hazra, Muralidhar L Hegde, Zsolt Radak, Attila Bacsi, Allan R Brasier, Xueqing Ba, Istvan Boldogh
A large percentage of redox-responsive gene promoters contain evolutionarily conserved guanine-rich clusters; guanines are the bases most susceptible to oxidative modification(s). Consequently, 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the most abundant base lesions in promoters and is primarily repaired via the 8-oxoguanine DNA glycosylase-1 (OOG1)-initiated base excision repair pathway. In view of a prompt cellular response to oxidative challenge, we hypothesized that the 8-oxoG lesion and the cognate repair protein OGG1 are utilized in transcriptional gene activation...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27662828/generation-and-characterization-of-a-novel-transgenic-mouse-harboring-conditional-nuclear-factor-kappa-b-rela-knockout-alleles
#20
Talha Ijaz, Maki Wakamiya, Hong Sun, Adrian Recinos, Ronald G Tilton, Allan R Brasier
BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to-mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of RelA leads to massive apoptosis of liver hepatocytes and death in utero. To study the role of RelA in physiology and in disease states in a manner that circumvents this embryonic lethal phenotype, we have generated a mouse with RelA conditional knockout (CKO) alleles containing loxP sites that are deleted by activated Cre recombinase...
September 23, 2016: BMC Developmental Biology
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