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https://www.readbyqxmd.com/read/28427148/in-depth-proteomic-profiling-of-left-ventricular-tissues-in-human-end-stage-dilated-cardiomyopathy
#1
Shanshan Liu, Yan Xia, Xiaohui Liu, Yi Wang, Zhangwei Chen, Juanjuan Xie, Juying Qian, Huali Shen, Pengyuan Yang
Dilated cardiomyopathy (DCM) is caused by reduced left ventricular (LV) myocardial function, which is one of the most common causes of heart failure (HF). We performed iTRAQ-coupled 2D-LC-MS/MS to profile the cardiac proteome of LV tissues from healthy controls and patients with end-stage DCM. We identified 4263 proteins, of which 125 were differentially expressed in DCM tissues compared to LV controls. The majority of these were membrane proteins related to cellular junctions and neuronal metabolism. In addition, these proteins were involved in membrane organization, mitochondrial organization, translation, protein transport, and cell death process...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410969/characterization-and-mechanism-of-phosphoinositide-3-kinases-pi3ks-members-in-insulin-induced-changes-of-protein-metabolism-in-yellow-catfish-pelteobagrus-fulvidraco
#2
Mei-Qin Zhuo, Yan-Xiong Pan, Kun Wu, Yi-Huan Xu, Zhi Luo
In the present study, seven phosphoinositide 3-kinase (PI3K) members (PI3KCa, PI3KCb, PI3KCd, PI3KCg, PI3KC2a, PI3KC2b and PI3KC3, respectively) were isolated and characterized from yellow catfish Pelteobagrus fulvidraco, and their roles in insulin-induced changes of protein metabolism were determined. These seven PI3Ks can be divided into three classes, class I (including PI3KCa, PI3KCb, PI3KCd and PI3KCg), class II (including PI3KC2a and PI3KC2b) and class III (only including PI3KC3). Compared with mammals, all of these members share similar domain structure...
April 11, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28345161/a-decrease-in-eukaryotic-elongation-factor-2-phosphorylation-is-required-for-local-translation-of-sensorin-and-long-term-facilitation-in-aplysia
#3
Patrick K McCamphill, Larissa Ferguson, Wayne S Sossin
Mechanistic target of rapamycin complex 1 (mTORC1)-dependent protein synthesis is required for many forms of synaptic plasticity and memory, but the downstream pathways important for synaptic plasticity are poorly understood. Long-term facilitation (LTF) in Aplysia is a form of synaptic plasticity that is closely linked to behavioural memory and an attractive model system for examining the important downstream targets for mTORC1 in regulating synaptic plasticity. While mTORC1 regulated protein synthesis has been strongly linked to translation initiation, translation elongation is also regulated by mTORC1 and LTF leads to an mTORC1 dependent decrease in eukaryotic elongation factor 2 (eEF2) phosphorylation...
March 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28245596/influence-of-dph1-and-dph5-protein-variants-on-the-synthesis-of-diphthamide-the-target-of-adpribosylating-toxins
#4
Klaus Mayer, Anna Schröder, Jerome Schnitger, Sebastian Stahl, Ulrich Brinkmann
The diphthamide on eukaryotic translation elongation factor 2 (eEF2) is the target of ADPribosylating toxins and -derivatives that serve as payloads in targeted tumor therapy. Diphthamide is generated by seven DPH proteins; cells deficient in these (DPHko) lack diphthamide and are toxin-resistant. We have established assays to address the functionality of DPH1 (OVCA1) and DPH5 variants listed in dbSNP and cosmic databases: plasmids encoding wildtype and mutant DPHs were transfected into DPHko cells. Supplementation of DPH1 and DPH5 restores diphthamide synthesis and toxin sensitivity in DPH1ko and DPH5ko cells, respectively...
February 24, 2017: Toxins
https://www.readbyqxmd.com/read/28237344/identification-and-evaluation-of-reference-genes-for-accurate-gene-expression-normalization-of-fresh-and-frozen-thawed-spermatozoa-of-water-buffalo-bubalus-bubalis
#5
Shende Ashish, S K Bhure, Pillai Harikrishna, S S Ramteke, V H Muhammed Kutty, N Shruthi, G V P P S Ravi Kumar, Mahawar Manish, S K Ghosh, Sarkar Mihir
The quantitative real time PCR (qRT-PCR) has become an important tool for gene-expression analysis for a selected number of genes in life science. Although large dynamic range, sensitivity and reproducibility of qRT-PCR is good, the reliability majorly depend on the selection of proper reference genes (RGs) employed for normalization. Although, RGs expression has been reported to vary considerably within same cell type with different experimental treatments. No systematic study has been conducted to identify and evaluate the appropriate RGs in spermatozoa of domestic animals...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28205128/heat-shock-protein-70-protects-cardiomyocytes-through-suppressing-sumoylation-and-nucleus-translocation-of-phosphorylated-eukaryotic-elongation-factor-2-during-myocardial-ischemia-and-reperfusion
#6
Chao Zhang, Xiaojuan Liu, Jin Miao, Shengcun Wang, Liucheng Wu, Daliang Yan, Jingjing Li, Wanwan Guo, Xiang Wu, Aiguo Shen
Myocardial ischemia and reperfusion (MIR) results in cardiomyocyte apoptosis with severe outcomes, which blocks cardiac tissue recovering from myocardial ischemia diseases. Heat shock protein 70 (HSP70) is one of protective molecule chaperones which could regulate the nucleus translocation of other proteins. In addition, eukaryotic elongation factor 2 (eEF2), which modulates protein translation process, is vital to the recovery of heart during MIR. However, the relationship between HSP70 and eEF2 and its effects on MIR are unclear...
February 15, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28186172/appropriateness-of-reference-genes-for-normalizing-messenger-rna-in-mouse-2-4-dinitrobenzene-sulfonic-acid-dnbs-induced-colitis-using-quantitative-real-time-pcr
#7
Nour Eissa, Laëtitia Kermarrec, Hayam Hussein, Charles N Bernstein, Jean-Eric Ghia
2,4-Dinitrobenzene sulfonic acid (DNBS)-induced colitis is an experimental model that mimics Crohn's disease. Appropriateness of reference genes is crucial for RT-qPCR. This is the first study to determine the stability of reference gene expression (RGE) in mice treated with DNBS. DNBS experimental Colitis was induced in male C57BL/6 mice. RNA was extracted from colon tissue and comprehensive analysis of 13 RGE was performed according to predefined criteria. Relative colonic TNF-α and IL-1β mRNA levels were calculated...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181167/adherence-to-mediterranean-diet-is-associated-with-methylation-changes-in-inflammation-related-genes-in-peripheral-blood-cells
#8
A Arpón, J I Riezu-Boj, F I Milagro, C Razquin, M A Martínez-González, D Corella, R Estruch, R Casas, M Fitó, E Ros, J Salas-Salvadó, J A Martínez
Epigenetic processes, including DNA methylation, might be modulated by environmental factors such as the diet, which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events. Meanwhile, Mediterranean diet (MedDiet) has demonstrated favourable effects on cardiovascular risk, blood pressure, inflammation and other complications related to excessive adiposity. Some of these effects could be mediated by epigenetic modifications. Therefore, the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells...
February 8, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28095607/heat-shock-protein-70-promotes-coxsackievirus-b3-translation-initiation-and-elongation-via-akt-mtorc1-pathway-depending-on-activation-of-p70s6k-and-cdc2
#9
Fengping Wang, Ye Qiu, Huifang M Zhang, Paul Hanson, Xin Ye, Guangze Zhao, Ronald Xie, Lei Tong, Decheng Yang
We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of internal ribosome entry site trans-acting factor lupus autoantigen protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28094500/chronic-mild-stress-induced-alterations-of-local-protein-synthesis-a-role-for-cognitive-impairment
#10
Francesca Calabrese, Paola Brivio, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Mariusz Papp, Marco A Riva
Depression, a major cause of disability worldwide, is characterized by a complex and heterogeneous symptomatology. With this respect, cognitive deterioration represents a major problem that has a strong impact on a patient's function. Thus, within the context of a depressive phenotype, it is important to characterize the mechanisms that sustain cognitive dysfunctions and may represent an important target for pharmacological intervention. Here, using the chronic mild stress (CMS) paradigm of depression, we found that, independently from the anhedonic phenotype, CMS rats showed a deficit in the novel object recognition (NOR) test, which is associated with an inability to phosphorylate GluN2B subunit on Ser1303 and to activate the mTOR pathway...
February 3, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28087840/vibrio-cholerae-cholix-toxin-induced-hepg2-cell-death-is-enhanced-by-tumor-necrosis-factor-alpha-through-ros-and-intracellular-signal-regulated-kinases
#11
Kohei Ogura, Yasuhiro Terasaki, Tohru Miyoshi-Akiyama, Mika Terasaki, Joel Moss, Masatoshi Noda, Kinnosuke Yahiro
Cholix toxin (Cholix) from Vibrio cholerae is a potent virulence factor exhibiting ADP-ribosyltransferase activity on eukaryotic elongation factor 2 (eEF2) of host cells, resulting in the inhibition of protein synthesis. Administration of Cholix or its homologue Pseudomonas exotoxin A (PEA) to mice causes lethal hepatocyte damage. In this study, we demonstrate cytotoxicity of Cholix on human hepatocytes in the presence of tumor necrosis factor α (TNF-α), which has been reported to play a fatal role in PEA administered to mice...
April 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28060762/eukaryotic-elongation-factor-2-is-a-prognostic-marker-and-its-kinase-a-potential-therapeutic-target-in-hcc
#12
Leona L Pott, Sascha Hagemann, Henning Reis, Kristina Lorenz, Thilo Bracht, Thomas Herold, Boris V Skryabin, Dominik A Megger, Julia Kälsch, Frank Weber, Barbara Sitek, Hideo A Baba
Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28013103/ebola-virus-vp35-blocks-stress-granule-assembly
#13
Valerie Le Sage, Alessandro Cinti, Stephen McCarthy, Raquel Amorim, Shringar Rao, Gian Luca Daino, Enzo Tramontano, Donald R Branch, Andrew J Mouland
Stress granules (SGs) are dynamic cytoplasmic aggregates of translationally silenced mRNAs that assemble in response to environmental stress. SGs appear to play an important role in antiviral innate immunity and many viruses have evolved to block or subvert SGs components for their own benefit. Here, we demonstrate that intracellular Ebola virus (EBOV) replication and transcription-competent virus like particles (trVLP) infection does not lead to SG assembly but leads to a blockade to Arsenite-induced SG assembly...
February 2017: Virology
https://www.readbyqxmd.com/read/28008374/comparative-proteomics-analysis-of-human-osteosarcoma-by-2d-dige-with-maldi-tof-tof-ms
#14
Guoxiang Wang, Zhengyao Zhang, Maoguang Yang, Bo Xu, Qi Gao, Xiaoyu Yang
Osteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. However, controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel protein targets will be critical to identify the path toward improving outcomes for patients...
November 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27940554/rna-helicase-ddx19-stabilizes-ribosomal-elongation-and-termination-complexes
#15
Tatiana Mikhailova, Ekaterina Shuvalova, Alexander Ivanov, Denis Susorov, Alexey Shuvalov, Peter M Kolosov, Elena Alkalaeva
The human DEAD-box RNA-helicase DDX19 functions in mRNA export through the nuclear pore complex. The yeast homolog of this protein, Dbp5, has been reported to participate in translation termination. Using a reconstituted mammalian in vitro translation system, we show that the human protein DDX19 is also important for translation termination. It is associated with the fraction of translating ribosomes. We show that DDX19 interacts with pre-termination complexes (preTCs) in a nucleotide-dependent manner. Furthermore, DDX19 increases the efficiency of termination complex (TC) formation and the peptide release in the presence of eukaryotic release factors...
December 9, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913948/branched-chain-amino-acids-administration-suppresses-endurance-exercise-related-activation-of-ubiquitin-proteasome-signaling-in-trained-human-skeletal-muscle
#16
Evgeny A Lysenko, Tatiana F Vepkhvadze, Egor M Lednev, Olga L Vinogradova, Daniil V Popov
We tested whether post exercise ingestion of branched-chain amino acids (BCAA < 10 g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1 g/kg). Post exercise ACC(Ser79/222) phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P < 0...
December 3, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27834892/towards-engineering-novel-pe-based-immunotoxins-by-targeting-them-to-the-nucleus
#17
Marta Borowiec, Michal Gorzkiewicz, Joanna Grzesik, Aurelia Walczak-Drzewiecka, Anna Salkowska, Ewelina Rodakowska, Kamil Steczkiewicz, Leszek Rychlewski, Jaroslaw Dastych, Krzysztof Ginalski
Exotoxin A (PE) from Pseudomonas aeruginosa is a bacterial ADP-ribosyltransferase, which can permanently inhibit translation in the attacked cells. Consequently, this toxin is frequently used in immunotoxins for targeted cancer therapies. In this study, we propose a novel modification to PE by incorporating the NLS sequence at its C-terminus, to make it a selective agent against fast-proliferating cancer cells, as a nucleus-accumulated toxin should be separated from its natural substrate (eEF2) in slowly dividing cells...
November 10, 2016: Toxins
https://www.readbyqxmd.com/read/27821870/disinhibition-of-somatostatin-positive-gabaergic-interneurons-results-in-an-anxiolytic-and-antidepressant-like-brain-state
#18
T Fuchs, S J Jefferson, A Hooper, P-Hp Yee, J Maguire, B Luscher
Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABAA receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic doses of ketamine. Thus GABAergic deficits may causally contribute to depressive disorders, while antidepressant therapies may enhance GABAergic synaptic transmission. Here we tested the hypothesis that sustained enhancement of GABAergic transmission alone is sufficient to elicit antidepressant-like behavior, using disinhibition of GABAergic interneurons...
November 8, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27780819/light-load-resistance-exercise-increases-muscle-protein-synthesis-and-hypertrophy-signaling-in-elderly-men
#19
Jakob Agergaard, Jacob Bülow, Jacob K Jensen, Søren Reitelseder, Micah J Drummond, Peter Schjerling, Thomas Scheike, Anja Serena, Lars Holm
The present study investigated whether well-tolerated light-load resistance exercise (LL-RE) affects skeletal muscle fractional synthetic rate (FSR) and anabolic intracellular signaling as a way to counteract age-related loss of muscle mass. Untrained healthy elderly (>65-yr-old) men were subjected to 13 h of supine rest. After 2.5 h of rest, unilateral LL-RE, consisting of leg extensions (10 sets, 36 repetitions) at 16% of 1 repetition maximum (RM), was conducted. Subsequently, the subjects were randomized to oral intake of 4 g of whey protein per hour (PULSE, n = 10), 28 g of whey protein at 0 h and 12 g of whey protein at 7 h postexercise (BOLUS, n = 10), or 4 g of maltodextrin per hour (placebo, n = 10)...
April 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27760376/discovery-of-new-substrates-of-the-elongation-factor-2-kinase-suggests-a-broader-role-in-the-cellular-nutrient-response
#20
Michael B Lazarus, Rebecca S Levin, Kevan M Shokat
Elongation Factor-2 Kinase (eEF2K) in an unusual mammalian enzyme that has one known substrate, elongation factor-2. It belongs to a class of kinases, called alpha kinases, that has little sequence identity to the >500 conventional protein kinases, but performs the same reaction and has similar catalytic residues. The phosphorylation of eEF2 blocks translation elongation, which is thought to be critical to regulating cellular energy usage. Here we report a system for discovering new substrates of alpha kinases and identify the first new substrates of eEF2K including AMPK and alpha4, and determine a sequence motif for the kinase that shows a requirement for threonine residues as the target of phosphorylation...
January 2017: Cellular Signalling
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