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https://www.readbyqxmd.com/read/27913676/translational-control-by-mtor-independent-routes-how-eif6-organizes-metabolism
#1
REVIEW
Annarita Miluzio, Sara Ricciardi, Nicola Manfrini, Roberta Alfieri, Stefania Oliveto, Daniela Brina, Stefano Biffo
Over the past few years, there has been a growing interest in the interconnection between translation and metabolism. Important oncogenic pathways, like those elicited by c-Myc transcription factor and mTOR kinase, couple the activation of the translational machinery with glycolysis and fatty acid synthesis. Eukaryotic initiation factor 6 (eIF6) is a factor necessary for 60S ribosome maturation. eIF6 acts also as a cytoplasmic translation initiation factor, downstream of growth factor stimulation. eIF6 is up-regulated in several tumor types...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911265/mirna-543-promotes-osteosarcoma-cell-proliferation-and-glycolysis-by-partially-suppressing-prmt9-and-stabilizing-hif-1%C3%AE-protein
#2
Heng Zhang, Xiaofeng Guo, Xing Feng, Tingting Wang, Zhaohua Hu, Xiangyong Que, Qingsong Tian, Tianbo Zhu, Guixian Guo, Wei Huang, Xinzhi Li
Osteosarcoma (OS) is the most common primary bone tumor, occurring frequently in adolescents and possessing a high malignant severity. MicroRNAs play critical roles during OS development. Thus, elucidation of the involvement of specific microRNAs in the development of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-543 were significantly increased whereas the levels of PRMT9 were significantly decreased, compared to the paired normal bone tissue...
November 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909264/global-ablation-of-the-mitochondrial-calcium-uniporter-increases-glycolysis-in-cortical-neurons-subjected-to-energetic-stressors
#3
Matthew Nichols, Pia A Elustondo, Jordan Warford, Aruloli Thirumaran, Evgeny V Pavlov, George S Robertson
The effects of global mitochondrial calcium (Ca(2+)) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca(2+) handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca(2+) uptake and Ca(2+)-induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage...
December 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27908246/inhibition-of-chaperonin-groel-by-a-monomer-of-ovine-prion-protein-and-its-oligomeric-forms
#4
S S Kudryavtseva, Y Y Stroylova, I A Zanyatkin, T Haertle, V I Muronetz
The possibility of inhibition of chaperonin functional activity by amyloid proteins was studied. It was found that the ovine prion protein PrP as well as its oligomeric and fibrillar forms are capable of binding with the chaperonin GroEL. Besides, GroEL was shown to promote amyloid aggregation of the monomeric and oligomeric PrP as well as PrP fibrils. The monomeric PrP was shown to inhibit the GroEL-assisted reactivation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The oligomers of PrP decelerate the GroEL-assisted reactivation of GAPDH, and PrP fibrils did not affect this process...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27907012/the-signature-of-microrna-dysregulation-in-muscle-paralyzed-by-spinal-cord-injury-includes-downregulation-of-micrornas-that-target-myostatin-signaling
#5
Rita De Gasperi, Zachary A Graham, Lauren M Harlow, William A Bauman, Weiping Qin, Christopher P Cardozo
Spinal cord injury (SCI) results in muscle atrophy, reduced force generation and an oxidative-to-glycolytic fiber type shift. The mechanisms responsible for these alterations remain incompletely understood. To gain new insights regarding mechanisms involved in deterioration of muscle after SCI, global expression profiles of miRs in paralyzed gastrocnemius muscle were compared between sham-operated (Sham) and spinal cord-transected (SCI) rats. Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes...
2016: PloS One
https://www.readbyqxmd.com/read/27906678/humoral-immune-responses-toward-tumor-derived-antigens-in-previously-untreated-patients-with-chronic-lymphocytic-leukemia
#6
Valentina Griggio, Giorgia Mandili, Candida Vitale, Michela Capello, Paolo Macor, Sara Serra, Barbara Castella, Silvia Peola, Myriam Foglietta, Daniela Drandi, Paola Omedé, Daniele Sblattero, Paola Cappello, Roberto Chiarle, Silvia Deaglio, Mario Boccadoro, Francesco Novelli, Massimo Massaia, Marta Coscia
In chronic lymphocytic leukemia (CLL) the occurrence and the impact of antibody responses toward tumor-derived antigens are largely unexplored. Our serological proteomic data show that antibodies toward 47 identified antigens are detectable in 29 out of 35 patients (83%) with untreated CLL. The glycolytic enzyme alpha-enolase (ENO1) is the most frequently recognized antigen (i.e. 54% of CLL sera). We show that ENO1 is upregulated in the proliferating B-cell fraction of CLL lymph nodes. In CLL cells of the peripheral blood, ENO1 is exclusively expressed at the intracellular level, whereas it is exposed on the surface of apoptotic leukemic cells...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#7
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906055/mesenchymal-stem-cells-multipotent-stromal-cells-mscs-are-glycolytic-and-thus-glucose-is-a-limiting-factor-of-in-vitro-models-of-msc-starvation
#8
Austin Nuschke, Melanie Rodrigues, Albin W Wells, Kyle Sylakowski, Alan Wells
BACKGROUND: Mesenchymal stem/multipotent stromal cells (MSCs) contribute to tissue repair but are challenged during wound healing when the blood supply is disrupted, thereby limiting nutrient delivery. Survival mechanisms against 'starvation' include autophagy, which we previously found to enhance differentiation efficiency. MSC response to models of in vitro nutrient deprivation are of great interest for improving MSC survival and therapeutic efficacy; however, the rate-limiting nutrients are unknown...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27904684/ldhb-may-be-a-significant-predictor-of-poor-prognosis-in-osteosarcoma
#9
Chao Li, Yu Chen, Pingping Bai, Jiaqiang Wang, Zhenhui Liu, Tao Wang, Qiqing Cai
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Lactate dehydrogenase (LDH) is considered as the key glycolytic enzyme and involved in tumor initiation and metabolism. Here, we firstly found that LDHB was highly expressed in osteosarcoma cell lines. Expression profiling indicated that LDHB mRNA was elevated in osteosarcoma tissues with metastasis versus without metastasis, and LDHB high expression predicted a poor prognosis in patients. After LDHB knockdown by siRNA transfection, cell growth and proliferation were inhibited and presented a dose-dependent cell death via MTT assay...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#10
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#11
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/27901298/biomimicry-promotes-the-efficiency-of-a-10-step-sequential-enzymatic-reaction-on-nanoparticles-converting-glucose-to-lactate
#12
Chinatsu Mukai, Lizeng Gao, Jacquelyn L Nelson, James P Lata, Roy Cohen, Lauren Wu, Meleana M Hinchman, Magnus Bergkvist, Robert W Sherwood, Sheng Zhang, Alexander J Travis
For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27899560/not5-dependent-co-translational-assembly-of-ada2-and-spt20-is-essential-for-functional-integrity-of-saga
#13
Sari Kassem, Zoltan Villanyi, Martine A Collart
Acetylation of histones regulates gene expression in eukaryotes. In the yeast Saccharomyces cerevisiae it depends mainly upon the ADA and SAGA histone acetyltransferase complexes for which Gcn5 is the catalytic subunit. Previous screens have determined that global acetylation is reduced in cells lacking subunits of the Ccr4-Not complex, a global regulator of eukaryotic gene expression. In this study we have characterized the functional connection between the Ccr4-Not complex and SAGA. We show that SAGA mRNAs encoding a core set of SAGA subunits are tethered together for co-translational assembly of the encoded proteins...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27894955/blocking-preferential-glucose-uptake-sensitizes-liver-tumor-initiating-cells-to-glucose-restriction-and-sorafenib-treatment
#14
Hui-Lu Zhang, Ming-Da Wang, Xu Zhou, Chen-Jie Qin, Gong-Bo Fu, Liang Tang, Han Wu, Shuai Huang, Ling-Hao Zhao, Min Zeng, Jiao Liu, Dan Cao, Lin-Na Guo, Hong-Yang Wang, He-Xin Yan, Jie Liu
Cancer cells display altered metabolic phenotypes characterized by a high level of glycolysis, even under normoxic conditions. Because of a high rate of glycolytic flux and inadequate vascularization, tumor cells often suffer from nutrient deficiency and require metabolic adaptations to address such stresses. Although tumor-initiating cells (T-ICs) have been identified in various malignancies, the cells' metabolic phenotypes remain elusive. In this study, we observed that liver T-ICs preferentially survived under restricted glucose treatment...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894844/the-tricarboxylic-acid-cycle-activity-in-cultured-primary-astrocytes-is-strongly-accelerated-by-the-protein-tyrosine-kinase-inhibitor-tyrphostin-23
#15
Michaela C Hohnholt, Eva-Maria Blumrich, Helle S Waagepetersen, Ralf Dringen
Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases and has been considered as potential anti-cancer drug. T23 was recently reported to acutely stimulate the glycolytic flux in primary cultured astrocytes. To investigate whether T23 also affects the tricarboxylic acid (TCA) cycle, we incubated primary rat astrocyte cultures with [U-(13)C]glucose in the absence or the presence of 100 μM T23 for 2 h and analyzed the (13)C metabolite pattern. These incubation conditions did not compromise cell viability and confirmed that the presence of T23 doubled glycolytic lactate production...
November 25, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27890797/3-bromopyruvate-treatment-induces-alterations-of-metabolic-and-stress-related-pathways-in-glioblastoma-cells
#16
Davide Chiasserini, Magdalena Davidescu, Pier Luigi Orvietani, Federica Susta, Lara Macchioni, Maya Petricciuolo, Emilia Castigli, Rita Roberti, Luciano Binaglia, Lanfranco Corazzi
: Glioblastoma (GBM) is the most common and aggressive brain tumours of adults. The metabolic phenotype of GBM cells is highly dependent on glycolysis; therefore, therapeutic strategies aimed at interfering with glycolytic pathways are under consideration. 3-Bromopyruvate (3BP) is a potent antiglycolytic agent, with a variety of targets and possible effects on global cell metabolism. Here we analyzed the changes in protein expression on a GBM cell line (GL15 cells) caused by 3BP treatment using a global proteomic approach...
November 23, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27889643/multimodality-imaging-identifies-distinct-metabolic-profiles-in-vitro-and-in-vivo
#17
Marie-Aline Neveu, Géraldine De Preter, Valérie Marchand, Anne Bol, Jeffery R Brender, Keita Saito, Shun Kishimoto, Paolo E Porporato, Pierre Sonveaux, Vincent Grégoire, Olivier Feron, Bénédicte F Jordan, Murali C Krishna, Bernard Gallez
The study of alterations of tumor metabolism should allow the identification of new targets for innovative anticancer strategies. Metabolic alterations are generally established in vitro, and conclusions are often extrapolated to the in vivo situation without further tumor metabolic phenotyping. To highlight the key role of microenvironment on tumor metabolism, we studied the response of glycolytic and oxidative tumor models to metabolic modulations in vitro and in vivo. MDA-MB-231 and SiHa tumor models, characterized in vitro as glycolytic and oxidative, respectively, were studied...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27885630/vesicular-glutamate-uptake
#18
Tetsufumi Ueda
Glutamate is an excitatory neurotransmitter widely used in the vertebrate central nervous systems. The synaptic transmission process is characterized by three steps: (1) presynaptic vesicular transmitter uptake, (2) presynaptic release, and (3) postsynaptic receptor activation. Presynaptic vesicular glutamate uptake plays an initial pivotal role in glutamate transmission by concentrating glutamate in the vesicular lumen prior to its release. This active glutamate transport harnesses energy derived from ATP hydrolysis, and intra- or extravesicular chloride, and is highly specific to glutamate...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27884962/triheptanoin-long-term-effects-in-the-very-long-chain-acyl-coa-dehydrogenase-vlcad-deficient-mouse
#19
Sara Tucci, Ulrich Floegel, Frauke Beermann, Sidney Behringer, Ute Spiekerkoetter
A rather new approach in the treatment of long-chain fatty acid oxidation disorders is represented by triheptanoin, a triglyceride with three medium-odd-chain heptanoic acid (C7) due to its anaplerotic potential. We here investigate the effects of a one-year triheptanoin-based diet on the clinical phenotype of very long-chain-acyl-CoA-dehydrogenase-deficient (VLCAD-/-) mice. The cardiac function was assessed in VLCAD-/- mice by in vivo MRI. Metabolic adaptations were identified by the expression of genes regulating energy metabolism and anaplerotic processes using real-time-PCR and the results were correlated with the measurement of the glycolytic enzymes pyruvate dehydrogenase (PDH) and pyruvate kinase (PK)...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27884166/tigar-cooperated-with-glycolysis-to-inhibit-the-apoptosis-of-leukemia-cells-and-associated-with-poor-prognosis-in-patients-with-cytogenetically-normal-acute-myeloid-leukemia
#20
Sixuan Qian, Jianyong Li, Ming Hong, Yu Zhu, Huihui Zhao, Yue Xie, Jiayu Huang, Yun Lian, Yanru Li, Shuai Wang, Jianping Mao, Yaoyu Chen
BACKGROUND: Cancer cells show increased glycolysis and take advantage of this metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from intracellular reactive oxygen species (ROS)-associated apoptosis. However, the function of TIGAR in glycolysis and survival of acute myeloid leukemia cells remains unclear. METHODS: We analyzed TIGAR expression in cytogenetically normal (CN-) AML patients and the correlations with clinical and biological parameters...
November 25, 2016: Journal of Hematology & Oncology
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