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https://www.readbyqxmd.com/read/29748184/dual-suppressive-effect-of-microrna-34a-on-the-foxm1-eef2-kinase-axis-regulates-triple-negative-breast-cancer-growth-and-invasion
#1
Recep Bayraktar, Cristina Ivan, Emine Bayraktar, Pinar Kanlikilicer, Nashwa Kabil, Nermin Kahraman, Hamada Ahmed Mokhlis, Didem Karakas, Cristian Rodriguez-Aguayo, Ahmet Arslan, Jianting Sheng, Stephen Tc Wong, Gabriel Lopez-Berestein, George A Calin, Bulent Ozpolat
Purpose - Recent studies indicated that dysregulation of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) is involved in pathogenesis of various human cancers. However, the molecular mechanisms underlying miR-34a are not fully understood in triple-negative breast cancer (TNBC). Experimental Design- We performed  in vitro  functional assays on TNBC cell lines to investigate the role of miR-34a in FOXM1/eEF2K signaling axis. TNBC tumor xenograft models were used for in vivo therapeutic delivery of miR-34a...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29736744/antidepressant-efficacy-and-tolerability-of-ketamine-and-esketamine-a-critical-review
#2
REVIEW
P Molero, J A Ramos-Quiroga, R Martin-Santos, E Calvo-Sánchez, L Gutiérrez-Rojas, J J Meana
Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to produce a rapid-onset antidepressant effect in treatment-resistant depression. Ketamine causes continued blockade of the glutamate N-methyl-D-aspartate (NMDA) receptor, though this might not primarily mediate the antidepressant effect. Alternative hypotheses include selectivity for the NMDA receptor subtype containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling pathway, alongside other independent actions attributed to the ketamine metabolism to R-hydroxynorketamine (R-HNK)...
May 7, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29736615/bdnf-reduces-eef2-phosphorylation-and-enhances-novel-protein-synthesis-in-the-growth-cones-of-dorsal-root-ganglia-neurons
#3
Osamu Hoshi, Ayana Sugizaki, Yuichiro Cho, Nobuyuki Takei
The local translation, which is regulated by extracellular stimuli such as guidance molecules, in growth cones of neurons provides a molecular mechanism for axonal development. In this study, we performed immunocytochemistry together with atomic force microscopy to investigate the localization of ribosomal proteins in the growth cones of rat dorsal root ganglion (DRG) neurons. The immunoreactivity of ribosomal protein P0/1/2 and S6, and novel protein synthesis were observed in the central, sterically bulky region of growth cones...
May 7, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29729916/short-communication-high-incubation-temperature-in-bovine-mammary-epithelial-cells-reduced-the-activity-of-the-mtor-signaling-pathway
#4
J D Kaufman, K R Kassube, R A Almeida, A G Ríus
Hyperthermia alters utilization of AA in protein synthesis and cell-signaling activity in bovine mammary cells. Essential AA and insulin regulate translation of proteins by controlling the activity of mammalian target of rapamycin (mTOR) signaling pathway. The objectives of this study were to evaluate (1) the effects of incubation temperature on the mTOR signaling pathway and transcription of AA transporters in a bovine mammary alveolar cell line (MAC-T) and (2) the combined effects of incubation temperature and insulin on the mTOR signaling pathway in this cell line...
May 2, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29700204/sunrise-measuring-translation-elongation-at-single-cell-resolution-by-flow-cytometry
#5
Rafael J Argüello, Marisa Reverendo Simoes, Andreia Mendes, Voahirana Camosseto, Adrian G Torres, Lluis Ribas de Pouplana, Serge A van de Pavert, Evelina Gatti, Philippe Pierre
The processing rate of translating ribosomes along mRNAs regulates gene expression by controling co-translational protein folding and mRNA stability. Many factors regulate translation elongation, including tRNA levels, codon usage, or phosphorylation of eukaryotic Elongation Factor 2 ( eEF2 ). Current methods to measure translation elongation lack single cell resolution, require expression of multiple transgenes and have never been successfully applied ex-vivo. Here, we show by using a combination of puromycilation detection and flow cytometry (SunRiSE), that translation elongation can be measured accurately in primary cells in pure or heterogenous populations isolated from blood or tissues...
April 26, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29550128/increasing-the-availability-of-threonine-isoleucine-valine-and-leucine-relative-to-lysine-while-maintaining-an-ideal-ratio-of-lysine-methionine-alters-mammary-cellular-metabolites-mammalian-target-of-rapamycin-signaling-and-gene-transcription
#6
X Dong, Z Zhou, L Wang, B Saremi, A Helmbrecht, Z Wang, J J Loor
Amino acids not only serve as precursors for protein synthesis but also function as signaling molecules that can regulate the mammalian target of rapamycin (mTOR) pathway. Methionine and Lys are the most-limiting AA for milk production and a ratio of ∼3:1 Lys:Met in the metabolizable protein has been determined to be ideal. Besides Met and Lys, recent studies have evaluated Ile, Leu, Val, and Thr as potentially limiting for milk protein synthesis. The objective of this experiment was to determine if varying the ratio of Lys:Thr, Lys:Ile, Lys:Val, and Lys:Leu while maintaining an ideal ratio of Lys:Met and fixed ratio of other essential AA (IPAA) elicits changes in intracellular metabolites, gene transcription related to protein synthesis, and phosphorylation status of mTOR pathway proteins...
June 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29532791/mechanisms-of-ketamine-action-as-an-antidepressant
#7
P Zanos, T D Gould
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine's widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine's antidepressant actions but lack its undesirable effects...
April 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29516301/convergent-mechanisms-underlying-rapid-antidepressant-action
#8
REVIEW
Panos Zanos, Scott M Thompson, Ronald S Duman, Carlos A Zarate, Todd D Gould
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites...
March 2018: CNS Drugs
https://www.readbyqxmd.com/read/29453282/eukaryotic-translation-elongation-factor-2-eef2-catalyzes-reverse-translocation-of-the-eukaryotic-ribosome
#9
Denis Susorov, Nikita Zakharov, Ekaterina Shuvalova, Alexander Ivanov, Tatiana Egorova, Alexey Shuvalov, Ivan N Shatsky, Elena Alkalaeva
During protein synthesis, a ribosome moves along the mRNA template and, using aminoacyl-tRNAs, decodes the template nucleotide triplets to assemble a protein amino acid sequence. This movement is accompanied by shifting of mRNA-tRNA complexes within the ribosome in a process called translocation. In living cells, this process proceeds in a unidirectional manner, bringing the ribosome to the 3' end of mRNA, and is catalyzed by the GTPase translation elongation factor 2 (EF-G in prokaryotes and eEF2 in eukaryotes)...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29435015/phosphoproteomic-analysis-of-the-antitumor-effects-of-ginsenoside-rg3-in-human-breast-cancer-cells
#10
Mingjin Zou, Jing Wang, Jidong Gao, Hui Han, Yi Fang
The incidence of breast cancer has been increasing in China and the age of breast cancer onset is earlier compared with Western countries. Compounds commonly used in Traditional Chinese Medicine (TCM) are an important source of anticancer drugs. Ginseng is one of the most common medicines used in TCM. Ginsenosides, which are saponins found in the ginseng plant, are the major active components responsible for the chemopreventive effects of ginseng in cancer. However, the mechanisms by which ginsenosides exert their anticancer effects remain elusive...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29431650/protein-translation-in-the-nucleus-accumbens-is-dysregulated-during-cocaine-withdrawal-and-required-for-expression-of-incubation-of-cocaine-craving
#11
Craig T Werner, Michael T Stefanik, Mike Milovanovic, Aaron Caccamise, Marina E Wolf
Exposure to drug-associated cues can induce drug craving and relapse in abstinent addicts. Cue-induced craving that progressively intensifies ("incubates") during withdrawal from cocaine has been observed in both rats and humans. Building on recent evidence that aberrant protein translation underlies incubation-related adaptations in the NAc, we used male rats to test the hypothesis that translation is dysregulated during cocaine withdrawal and/or when rats express incubated cocaine craving. We found that intra-NAc infusion of anisomycin, a general protein translation inhibitor, or rapamycin, an inhibitor of mammalian target of rapamycin, reduced the expression of incubated cocaine craving, consistent with previous results showing that inhibition of translation in slices normalized the adaptations that maintain incubation...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29397070/microrna-181a-downregulates-deptor-for-tgf%C3%AE-induced-glomerular-mesangial-cell-hypertrophy-and-matrix-protein-expression
#12
Soumya Maity, Amit Bera, Nandini Ghosh-Choudhury, Falguni Das, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
TGFβ contributes to mesangial cell hypertrophy and matrix protein increase in various kidney diseases including diabetic nephropathy. Deptor is an mTOR-interacting protein and suppresses mTORC1 and mTORC2 activities. We have recently shown that TGFβ-induced inhibition of deptor increases the mTOR activity. The mechanism by which TGFβ regulates deptor expression is not known. Here we identify deptor as a target of the microRNA-181a. We show that in mesangial cells, TGFβ increases the expression of miR-181a to downregulate deptor...
March 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29395043/calcium-calmodulin-dependent-protein-kinase-ii-and-eukaryotic-elongation-factor-2-kinase-pathways-mediate-the-antidepressant-action-of-ketamine
#13
Chinnakkaruppan Adaikkan, Elham Taha, Iliana Barrera, Orit David, Kobi Rosenblum
BACKGROUND: Ketamine is an N-methyl-D-aspartate receptor antagonist, which on administration produces fast-acting antidepressant responses in patients with major depressive disorder. Yet, the mechanism underlying the antidepressant action of ketamine remains unclear. METHODS: To unravel the mechanism of action of ketamine, we treated wild-type C57BL/6 mice with calcium/calmodulin-dependent protein kinase II (CaMKII) specific inhibitor tatCN21 peptide. We also used eukaryotic elongation factor 2 kinase (eEF2K) (also known as CaMKIII) knockout mice...
December 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29365377/-identification-and-analysis-of-the-proteins-interacted-with-prestin-in-cochlear-outer-hair-cells-of-guinea-pig
#14
X Luo, J Y Wang, F L Zhang, Y Xia
Objective: To explore the regulation and mechanism of Prestin protein by identifying the proteins interacted with Prestin in cochlear outer hair cell(OHC) and analyzing their biological function. Methods: Co-immunoprecipitation combined mass spectrometry technology was used to isolate and identify the proteins interacted with Prestin protein of OHC, bioinformatics was used to construct Prestin protein interaction network. The proteins interacted with Prestin in OHC of guinea pig were determined by matching primary interaction mass spectrometry with protein interaction network, and annotated their functions...
January 7, 2018: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/29362492/novel-compound-heterozygous-dph1-mutations-in-a-patient-with-the-unique-clinical-features-of-airway-obstruction-and-external-genital-abnormalities
#15
Junya Nakajima, Shingo Oana, Tomohiro Sakaguchi, Mitsuko Nakashima, Hironao Numabe, Hisashi Kawashima, Naomichi Matsumoto, Noriko Miyake
The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901)...
April 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29342219/the-expression-profile-and-prognostic-significance-of-eukaryotic-translation-elongation-factors-in-different-cancers
#16
Md Khurshidul Hassan, Dinesh Kumar, Monali Naik, Manjusha Dixit
Eukaryotic translation factors, especially initiation factors have garnered much attention with regards to their role in the onset and progression of different cancers. However, the expression levels and prognostic significance of translation elongation factors remain poorly explored in different cancers. In this study, we have investigated the mRNA transcript levels of seven translation elongation factors in different cancer types using Oncomine and TCGA databases. Furthermore, we have identified the prognostic significance of these factors using Kaplan-Meier Plotter and SurvExpress databases...
2018: PloS One
https://www.readbyqxmd.com/read/29337352/genetic-removal-of-eif2%C3%AE-kinase-perk-in-mice-enables-hippocampal-l-ltp-independent-of-mtorc1-activity
#17
Helena R Zimmermann, Wenzhong Yang, Brenna C Beckelman, Nicole P Kasica, Xueyan Zhou, Lucas Galli, Alexey G Ryazanov, Tao Ma
Characterization of the molecular signaling pathways underlying protein synthesis-dependent forms of synaptic plasticity, such as late long-term potentiation (L-LTP), can provide insights not only into memory expression/maintenance under physiological conditions but also potential mechanisms associated with the pathogenesis of memory disorders. Here, we report in mice that L-LTP failure induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2α (eIF2α)...
January 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29300771/demonstration-of-translation-elongation-factor-3-activity-from-a-non-fungal-species-phytophthora-infestans
#18
Maria K Mateyak, Justyna K Pupek, Alexandra E Garino, McCllelan C Knapp, Sarah F Colmer, Terri Goss Kinzy, Stephen Dunaway
In most eukaryotic organisms, translation elongation requires two highly conserved elongation factors eEF1A and eEF2. Fungal systems are unique in requiring a third factor, the eukaryotic Elongation Factor 3 (eEF3). For decades, eEF3, a ribosome-dependent ATPase, was considered "fungal-specific", however, recent bioinformatics analysis indicates it may be more widely distributed among other unicellular eukaryotes. In order to determine whether divergent eEF3-like proteins from other eukaryotic organisms can provide the essential functions of eEF3 in budding yeast, the eEF3-like proteins from Schizosaccharomyes pombe and an oomycete, Phytophthora infestans, were cloned and expressed in Saccharomyces cerevisiae...
2018: PloS One
https://www.readbyqxmd.com/read/29288744/metabolic-suppression-in-the-pelagic-crab-pleuroncodes-planipes-in-oxygen-minimum-zones
#19
Brad A Seibel, Bryan E Luu, Shannon N Tessier, Trisha Towanda, Kenneth B Storey
The pelagic red crab, Pleuroncodes planipes, is abundant throughout the Eastern Tropical Pacific in both benthic and pelagic environments to depths of several hundred meters. The oxygen minimum zones in this region reaches oxygen levels as low as 0.1kPa at depths within the crabs vertical range. Crabs maintain aerobic metabolism to a critical PO2 of ~0.27±0.2kPa (10°C), in part by increasing ventilation as oxygen declines. At subcritical oxygen levels, they enhance anaerobic ATP production slightly as indicated by modest increases in lactate levels...
December 27, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29283292/morphological-molecular-and-hormonal-adaptations-to-early-morning-versus-afternoon-resistance-training
#20
Milan Sedliak, Michal Zeman, Gabriel Buzgó, Jan Cvecka, Dusan Hamar, Eugen Laczo, Monika Okuliarova, Marian Vanderka, Tomas Kampmiller, Keijo Häkkinen, Juha P Ahtiainen, Juha J Hulmi, Tormod S Nilsen, Håvard Wiig, Truls Raastad
It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance...
December 28, 2017: Chronobiology International
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