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https://www.readbyqxmd.com/read/27924264/specificity-of-broad-protein-interaction-surfaces-for-proteins-with-multiple-binding-partners
#1
Nobuyuki Uchikoga, Yuri Matsuzaki, Masahito Ohue, Yutaka Akiyama
Analysis of protein-protein interaction networks has revealed the presence of proteins with multiple interaction ligand proteins, such as hub proteins. For such proteins, multiple ligands would be predicted as interacting partners when predicting all-to-all protein-protein interactions (PPIs). In this work, to obtain a better understanding of PPI mechanisms, we focused on protein interaction surfaces, which differ between protein pairs. We then performed rigid-body docking to obtain information of interfaces of a set of decoy structures, which include many possible interaction surfaces between a certain protein pair...
2016: Biophysics and Physicobiology
https://www.readbyqxmd.com/read/27918543/ficd-acts-bifunctionally-to-ampylate-and-de-ampylate-the-endoplasmic-reticulum-chaperone-bip
#2
Steffen Preissler, Claudia Rato, Luke A Perera, Vladimir Saudek, David Ron
Protein folding homeostasis in the endoplasmic reticulum (ER) is defended by an unfolded protein response that matches ER chaperone capacity to the burden of unfolded proteins. As levels of unfolded proteins decline, a metazoan-specific FIC-domain-containing ER-localized enzyme (FICD) rapidly inactivates the major ER chaperone BiP by AMPylating T518. Here we show that the single catalytic domain of FICD can also release the attached AMP, restoring functionality to BiP. Consistent with a role for endogenous FICD in de-AMPylating BiP, FICD(-/-) hamster cells are hypersensitive to introduction of a constitutively AMPylating, de-AMPylation-defective mutant FICD...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27905509/the-er-stress-regulator-bip-mediates-cadmium-induced-autophagy-and-neuronal-senescence
#3
Tao Wang, Yan Yuan, Hui Zou, Jinlong Yang, Shiwen Zhao, Yonggang Ma, Yi Wang, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Zongping Liu, Jiaqiao Zhu
Autophagy is protective in cadmium (Cd)-induced oxidative damage. Endoplasmic reticulum (ER) stress has been shown to induce autophagy in a process requiring the unfolded protein response signalling pathways. Cd treatment significantly increased senescence in neuronal cells, which was aggravated by 3-MA or silencing of Atg5 and abolished by rapamycin. Cd increased expression of ER stress regulators Bip, chop, eIf2α, and ATF4, and activated autophagy as evidenced by upregulated LC3. Moreover, the ER stress inhibitor mithramycin inhibited the expression of ER stress protein chaperone Bip and blocked autophagic flux...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#4
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
https://www.readbyqxmd.com/read/27888615/unconjugated-secondary-bile-acids-activate-the-unfolded-protein-response-and-induce-golgi-fragmentation-via-a-src-kinase-dependant-mechanism
#5
Ruchika Sharma, Francis Quilty, John F Gilmer, Aideen Long, Anne-Marie Byrne
Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27853103/endoplasmic-reticulum-stress-is-involved-in-2-4-dichlorophenol-induced-hepatotoxicity
#6
Jianbo Fu, Xiaoning Zhang, Peng Chen, Yingmei Zhang
2,4-Dichlorophenol (2,4-DCP) is an environmental pollutant exhibiting a wide spectrum of toxic effects. We investigated the toxic effects and potential mechanisms underlying 2,4-DCP-induced hepatotoxicity. In vitro, 2,4-DCP caused hepatotoxicity manifested by a decrease in cell viability and inhibition of colony formation. Bip and CHOP expression was up-regulated at the mRNA and protein levels. Moreover, 2,4-DCP induced eIF2α phosphorylation and Xbp1 mRNA splicing, indicating that endoplasmic reticulum (ER) stress was activated after exposure of HL7702 cells to 2,4-DCP for 12 hr...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27849634/inflammation-and-apoptosis-dual-mediator-role-for-toll-like-receptor-4-in-the-development-of-necrotizing-enterocolitis
#7
Yin Zhou, Yibo Li, Bin Zhou, Keling Chen, Zhaoying Lyv, Dongmei Huang, Bin Liu, Zhicheng Xu, Bo Xiang, Shuguang Jin, Xiaofeng Sun, Yuan Li
BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process...
November 14, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27846758/ankylosing-spondylitis-m-csf-derived-macrophages-are-undergoing-unfolded-protein-response-upr-and-express-higher-levels-of-interleukin-23
#8
Alireza Rezaiemanesh, Mahdi Mahmoudi, Ali Akbar Amirzargar, Mahdi Vojdanian, Ahmad Reza Jamshidi, Mohammad Hossein Nicknam
OBJECTIVE: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23. METHODS: Peripheral blood monocyte isolated from 10 HLA-B27(+) patients and 5 HLA-B27(+) normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days...
November 16, 2016: Modern Rheumatology
https://www.readbyqxmd.com/read/27830010/glutaminase-inhibitor-compound-968-inhibits-cell-proliferation-and-sensitizes-paclitaxel-in-ovarian-cancer
#9
Lingqin Yuan, Xiugui Sheng, Leslie H Clark, Lu Zhang, Hui Guo, Hannah M Jones, Adam K Willson, Paola A Gehrig, Chunxiao Zhou, Victoria L Bae-Jump
Our overall goal was to investigate the anti-tumor activity of the glutaminase 1 (GLS1) Inhibitor compound 968 in ovarian cancer cells. The human ovarian cancer cell lines, HEY, SKOV3 and IGROV-1 were used. Cell proliferation was assessed by MTT assay after treatment with compound 968. Cell cycle progression and Annexin V expression were evaluated using Cellometer. Western blotting was performed to determine changes in GLS1, cellular stress and cell cycle checkpoints. Reactive oxygen species (ROS) and glutamate dehydrogenase (GDH) activity were assessed by ELISA assay...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27818117/-induced-abortion-guidelines-for-clinical-practice%C3%A2-%C3%A2-text-of-the-guidelines-short-text
#10
C Vayssière, A Gaudineau, L Attali, K Bettahar, S Eyraud, P Faucher, P Fournet, D Hassoun, M Hatchuel, C Jamin, B Letombe, T Linet, M Msika Razon, A Ohanessian, H Segain, S Vigoureux, N Winer, S Wylomanski, A Agostini
OBJECTIVE: Develop recommendations for the practice of induced abortion. MATERIALS AND METHODS: The Pubmed database, the Cochrane Library and the recommendations from the French and foreign Gyn-Obs societies or colleges have been consulted. RESULTS: The number of induced abortions (IA) has been stable for several decades. There are a lot of factors explaining the choice of abortion when there is an unplanned pregnancy (UPP). Early initiation and choice of contraception in connection to the woman's life are associated with lower NSP...
December 2016: Journal de Gynécologie, Obstétrique et Biologie de la Reproduction
https://www.readbyqxmd.com/read/27813270/endoplasmic-reticulum-stress-contributes-to-ferritin-molecules-mediated-macrophage-migration-via-p-selectin-glycoprotein-ligand-1
#11
Chi-Mei Wang, Yue-Hwa Chen, Yu-Chieh Lee, Jung-Su Chang
SCOPE: Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. METHODS AND RESULTS: Serum ferritin and soluble P-selectin glycoprotein ligand (sPSGL)-1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL-1 (B = 0...
November 4, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27809497/improved-performance-of-loop-mediated-isothermal-amplification-assays-via-swarm-priming
#12
Rhett L Martineau, Sarah Anne Murray, Shufang Ci, Weimin Gao, Shih-Hui Chao, Deirdre R Meldrum
This work describes an enhancement to the loop-mediated isothermal amplification (LAMP) reaction which results in improved performance. Enhancement is achieved by adding a new set of primers to conventional LAMP reactions. These primers are termed 'Swarm primers' based on their relatively high concentration and their ability to create new amplicons despite the theoretical lack of single-stranded annealing sites. The primers target a region upstream of the FIP/BIP primer recognition sequences on opposite strands, substantially overlapping F1/B1 sites...
November 4, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27809414/salidroside-protects-against-homocysteine-induced-injury-in-huvecs-via-the-regulation-of-endoplasmic-reticulum-stress
#13
Lin Zhu, Fang Jia, Jiang Wei, Yang Yu, Tianhong Yu, Yanjun Wang, Jianhui Sun, Guanghua Luo
INTRODUCTION: Previous studies showed that homocysteine(Hcy) could injure vascular endothelial cells via several mechanisms, including its promotion of oxidative stress pathway and endoplasmic reticulum stress (ER-stress) pathway. Salidroside(SAL) is an active component of Rhodiola rosea with documented antioxidative properties. Emerging evidence conformed that SAL attenuated Hcy induced endothelial dysfunction by reducing oxidative stress. However, its role in ER-stress pathway remains un-clarified...
November 3, 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27800636/diagnostic-value-of-autoantibodies-combined-detection-for-rheumatoid-arthritis
#14
Pingping Sun, Wanhai Wang, Ling Chen, Nan Li, Xianchun Meng, Jing Bian, Jingjing Yang, Xu'na Wang, Weitao Zhu, Liang Ming
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disease, there are many autoantibodies produced during disease progression in the patients' serum, and this work is to select a best detection scheme for RA diagnosis. METHODS: Autoantibody levels including rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), mutated citrullinated vimentin (MCV), anti-keratin antibodies(AKA), anti-perinuclear factor (APF), and Ig heavy chain binding protein (BIP), were measured, and the sensitivity, specificity, predictive values, accuracy, and Youden's index of different combining forms were all calculated in RA patients, disease, and healthy control group...
November 1, 2016: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/27796874/in-vitro-and-in-vivo-anticancer-activity-of-sophorolipids-to-human-cervical-cancer
#15
Hui Li, Wei Guo, Xiao-Jing Ma, Jia-Shan Li, Xin Song
Six characteristic di-acetylated lactonic sophorolipids with C16:1, C16:0, C18:0, C18:1, C18:2, and C18:3 fatty acid were obtained from Starmerella bombicola CGMCC 1576. In order to confirm their anticancer activity against human cervical cancer cells and reveal the structure-activity relationships, their anti-proliferation effects on HeLa and CaSki cells were estimated. The cytotoxicity of sophorolipid molecules with different degrees of unsaturation was proved to be influenced by carbon chain length of sophorolipids...
October 29, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27796797/sublethal-endoplasmic-reticulum-stress-caused-by-the-mutation-of-immunoglobulin-heavy-chain-binding-protein-induces%C3%A2-the-synthesis-of-a-mitochondrial-protein-pyrroline-5-carboxylate-reductase-1
#16
Hisayo Jin, Mari Komita, Haruhiko Koseki, Tomohiko Aoe
Most human neurodegenerative diseases are sporadic and appear later in life. Aging and neurodegeneration are closely associated, and recent investigations reveal that endoplasmic reticulum (ER) stress is involved in the progression of these features. Immunoglobulin heavy chain-binding protein (BiP) is an ER chaperone that is central to ER functions. We produced knock-in mice expressing a mutant BiP that lacked the retrieval sequence to elucidate the effect of a functional defect in an ER chaperone in multicellular organisms...
October 28, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27792754/characterization-of-zebrafish-models-of-marinesco-sj%C3%A3-gren-syndrome
#17
Genri Kawahara, Yukiko K Hayashi
SIL1 is a nucleotide exchange factor for the endoplasmic reticulum chaperone, BiP. Mutations in the SIL1 gene cause Marinesco-Sjögren syndrome (MSS), an autosomal recessive disease characterized by cerebellar ataxia, mental retardation, congenital cataracts, and myopathy. To create novel zebrafish models of MSS for therapeutic drug screening, we analyzed phenotypes in sil1 knock down fish by two different antisense oligo morpholinos. Both sil1 morphants had abnormal formation of muscle fibers and irregularity of the myosepta...
2016: PloS One
https://www.readbyqxmd.com/read/27791469/new-anti-cancer-molecules-targeting-hspa5-bip-to-induce-endoplasmic-reticulum-stress-autophagy-and-apoptosis
#18
Michaël Cerezo, Stéphane Rocchi
Treatment of melanoma has significantly advanced over the last decade, with the development of targeted therapies against the MAPK pathway and immunotherapies to reactivate antitumor immunity. Unfortunately, currently more than 50% of patients are in treatment failure. Thus, identification of new common cellular vulnerability among melanoma cells is an urgent need and will help in the discovery of more efficient treatments against melanoma. We have focused our study on protein processing and have identified a new compound, HA15, targeting HSPA5/BiP, the master regulator of the unfolded protein response (UPR)...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27784237/the-roles-of-endoplasmic-reticulum-stress-in-the-pathophysiological-development-of-cartilage-and-chondrocytes
#19
Xiaoliang Yuan, Haiqing Liu, Linfu Li, Hai Liu, Jianqiong Yang, Weimei Shi, Longhuo Wu
Endoplasmic reticulum (ER) has evolved an adaptive mechanism called unfolded protein response (UPR) at the initial stage to restore cellular homeostasis. The three ER transmembrane sensors, including IRE1α, PERK, and ATF6 are the key factors to decide cell fates. They exhibit both advantageous and disadvantageous effects, which depending on the micro-environmental state of cells. ER stress has been implicated in chondrocytes proliferation, differentiation, and hypertrophy through regulating transcriptional factors SOX9, Ihh, BMP-2, RUNX, and HIF1/2α...
October 25, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27769873/mitochondrial-proteomic-alterations-caused-by-long-term-low-dose-copper-exposure-in-mouse-cortex
#20
Xuemei Lin, Gang Wei, Zhijun Huang, Zhongsen Qu, Xinfeng Huang, Hua Xu, Jianjun Liu, Zhixiong Zhuang, Xifei Yang
Mitochondrial dysfunction is involved in neurotoxicity caused by exposure of various chemicals such as copper. However, the effects of long-term low-dose copper exposure on mitochondrial proteome remain unclear. In this study, we found the treatment of copper (0.13ppm copper sulfate in drinking water) for 12 months caused abnormal expression of a total of 13 mitochondrial proteins (7 up-regulated and 6 down-regulated) as revealed by two-dimensional electrophoresis coupled with mass spectrometry in mouse cortex...
October 18, 2016: Toxicology Letters
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