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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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 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 immortalized 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...
January 13, 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
#7
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...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28013103/ebola-virus-vp35-blocks-stress-granule-assembly
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
Jakob Agergaard, Jacob Bulow, Jacob K Jensen, Søren Reitelseder, Micah J Drummond, Peter Schjerling, Thomas Scheike, Anja Serena, Lars Holm
INTRODUCTION: 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. METHODS: Untrained healthy men (age: +65 yrs) were subjected to 13 hours supine rest. After 21/2 hours of rest, unilateral LL-RE was conducted consisting of leg extensions (10 sets, 36 repetitions) at 16% 1RM. Subsequently, the subjects were randomized to oral intake of PULSE (4g whey protein/hour; N=10), BOLUS (28g whey protein at 0 hours and 12g whey protein at 7 hours post-exercise; N=10) or placebo (4g maltodextrin/hour; N=10)...
October 25, 2016: 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
#15
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
https://www.readbyqxmd.com/read/27689327/low-carbohydrate-diet-prevents-mcl-1-mediated-resistance-to-bh3-mimetics
#16
Camila Rubio-Patiño, Jozef P Bossowski, Elodie Villa, Laura Mondragón, Barbara Zunino, Emma Proïcs, Johanna Chiche, Frédéric Bost, Els Verhoeyen, Jean-Ehrland Ricci
Overexpression of Mcl-1 is implicated in resistance of several cancers to chemotherapeutic treatment, therefore identifying a safe way to decrease its expression in tumor cells represents a central goal. We investigated if a modulation of the diet could impact on Mcl-1 expression using a Myc-driven lymphoma model. We established that a partial reduction of caloric intake by 25% represents an efficient way to decrease Mcl-1 expression in tumor cells. Furthermore, using isocaloric custom diets, we observed that carbohydrates (CHO) are the main regulators of Mcl-1 expression within the food...
8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27572820/pharmacological-eef2k-activation-promotes-cell-death-and-inhibits-cancer-progression
#17
Aude De Gassart, Olivier Demaria, Rébecca Panes, Léa Zaffalon, Alexey G Ryazanov, Michel Gilliet, Fabio Martinon
Activation of the elongation factor 2 kinase (eEF2K) leads to the phosphorylation and inhibition of the elongation factor eEF2, reducing mRNA translation rates. Emerging evidence indicates that the regulation of factors involved in protein synthesis may be critical for controlling diverse biological processes including cancer progression. Here we show that inhibitors of the HIV aspartyl protease (HIV-PIs), nelfinavir in particular, trigger a robust activation of eEF2K leading to the phosphorylation of eEF2...
October 2016: EMBO Reports
https://www.readbyqxmd.com/read/27525663/structures-properties-and-dynamics-of-intermediates-in-eef2-diphthamide-biosynthesis
#18
Jean-Marc Billod, Patricia Saenz-Mendez, Anders Blomberg, Leif A Eriksson
The eukaryotic translation Elongation Factor 2 (eEF2) is an essential enzyme in protein synthesis. eEF2 contains a unique modification of a histidine (His699 in yeast; HIS) into diphthamide (DTA), obtained via 3-amino-3-carboxypropyl (ACP) and diphthine (DTI) intermediates in the biosynthetic pathway. This essential and unique modification is also vulnerable, in that it can be efficiently targeted by NAD(+)-dependent ADP-ribosylase toxins, such as diphtheria toxin (DT). However, none of the intermediates in the biosynthesis path is equally vulnerable against the toxins...
September 26, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/27510652/interleukin-1%C3%AE-effect-on-the-endogenous-adp-ribosylation-and-phosphorylation-of-eukaryotic-elongation-factor-2
#19
Ebru Hacıosmanoğlu, Başak Varol, Bilge Özerman Edis, Muhammet Bektaş
Eukaryotic elongation factor 2 (eEF2) plays an important role in eukaryotic polypeptide chain elongation. Adenosine diphosphate (ADP)-ribosylation is a post-translational modification reaction that catalyzes the transfer of ADP-ribose group to eEF2 and this causes the inhibition of protein synthesis. Indeed, in the absence of diptheria toxin, endogenous ADP-ribosylation can occur. eEF2 is phosphorylated by eEF2 kinase which prevents binding to ribosomes thus inhibiting its activity. Increase in endogenous ADP-ribosylation level approximately 70-75 % was observed in IL-1β treated HUVECs...
December 2016: Cytotechnology
https://www.readbyqxmd.com/read/27464336/decreased-whole-body-fat-mass-produced-by-chronic-alcohol-consumption-is-associated-with-activation-of-s6k1-mediated-protein-synthesis-and-increased-autophagy-in-epididymal-white-adipose-tissue
#20
Kristen T Crowell, Jennifer L Steiner, Catherine S Coleman, Charles H Lang
BACKGROUND: Chronic alcohol consumption leads to a loss of white adipose tissue (WAT) but the underlying mechanisms for this lipodystrophy are not fully elucidated. This study tested the hypothesis that the reduction in WAT mass in chronic alcohol-fed mice is associated with a decreased protein synthesis specifically related to impaired function of mammalian target of rapamycin (mTOR). METHODS: Adult male mice were provided an alcohol-containing liquid diet for 24 weeks or an isonitrogenous isocaloric control diet...
September 2016: Alcoholism, Clinical and Experimental Research
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