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https://www.readbyqxmd.com/read/28636461/genice-a-novel-framework-for-gene-network-inference-by-clustering-exhaustive-search-and-multivariate-analysis
#1
Ricardo de Souza Jacomini, David Correa Martins-Jr, Felipe Leno da Silva, Anna Helena Reali Costa
Gene network (GN) inference from temporal gene expression data is a crucial and challenging problem in systems biology. Expression data sets usually consist of dozens of temporal samples, while networks consist of thousands of genes, thus rendering many inference methods unfeasible in practice. To improve the scalability of GN inference methods, we propose a novel framework called GeNICE, based on probabilistic GNs; the main novelty is the introduction of a clustering procedure to group genes with related expression profiles and to provide an approximate solution with reduced computational complexity...
June 21, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28633139/mitochondrial-metabolism-in-a-large-animal-model-of-huntington-disease-the-hunt-for-biomarkers-in-the-spermatozoa-of-presymptomatic-minipigs
#2
Jana Krizova, Hana Stufkova, Marie Rodinova, Monika Macakova, Bozena Bohuslavova, Daniela Vidinska, Jiri Klima, Zdenka Ellederova, Antonin Pavlok, David S Howland, Jiri Zeman, Jan Motlik, Hana Hansikova
BACKGROUND: Huntington disease (HD) is a fatal neurodegenerative disorder involving reduced muscle coordination, mental and behavioral changes, and testicular degeneration. In order to further clarify the decreased fertility and penetration ability of the spermatozoa of transgenic HD minipig boars (TgHD), we applied a set of mitochondrial metabolism (MM) parameter measurements to this promising biological material, which can be collected noninvasively in longitudinal studies. OBJECTIVE: We aimed to optimize methods for MM measurements in spermatozoa and to establish possible biomarkers of HD in TgHD spermatozoa expressing the N-terminal part of mutated human huntingtin...
June 21, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28630480/pro-invasive-stimuli-and-the-interacting-protein-hsp70-favour-the-route-of-alpha-enolase-to-the-cell-surface
#3
Giovanni Perconti, Cristina Maranto, Daniele P Romancino, Patrizia Rubino, Salvatore Feo, Antonella Bongiovanni, Agata Giallongo
Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to the motility and invasiveness of cancer cells through the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation. Although a few recent records indicate the involvement of protein partners in the localization of alpha-enolase to the plasma membrane, the cellular mechanisms underlying surface exposure remain largely elusive. Searching for novel interactors and signalling pathways, we used low-metastatic breast cancer cells, a doxorubicin-resistant counterpart and a non-tumourigenic mammary epithelial cell line...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627164/thermodynamic-and-structural-adaptation-differences-between-the-mesophilic-and-psychrophilic-lactate-dehydrogenases
#4
Sergei Khrapunov, Eric P Chang, Robert Callender
The thermodynamics of substrate binding and enzymatic activity of a glycolytic enzyme, lactate dehydrogenase (LDH), from both porcine heart, phLDH (Sus scrofa; a mesophile), and from mackerel icefish, cgLDH (Chamapsocephalus gunnari; a psychrophile), were investigated. Using a novel and quite sensitive fluorescence assay which can distinguish protein conformational changes close and distal from the substrate binding pocket, a reversible global protein structural transition preceding the high-temperature transition (denaturation) was surprisingly found to coincide with a marked change in enzymatic activity for both LDHs...
June 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28626035/cyclin-d3-cdk6-has-a-metabolic-prosurvival-role-in-t-all
#5
(no author information available yet)
Cyclin D3-CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28625348/metabolic-regulation-of-the-pmca-role-in-cell-death-and-survival
#6
REVIEW
Jason I E Bruce
The plasma membrane Ca(2+)-ATPase (PMCA) is a ubiquitously expressed, ATP-driven Ca(2+) pump that is critical for maintaining low resting cytosolic Ca(2+) ([Ca(2+)]i) in all eukaryotic cells. Since cytotoxic Ca(2+) overload has such a central role in cell death, the PMCA represents an essential "linchpin" for the delicate balance between cell survival and cell death. In general, impaired PMCA activity and reduced PMCA expression leads to cytotoxic Ca(2+) overload and Ca(2+) dependent cell death, both apoptosis and necrosis, whereas maintenance of PMCA activity or PMCA overexpression is generally accepted as being cytoprotective...
June 8, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28624704/maintenance-of-redox-homeostasis-by-hypoxia-inducible-factors
#7
REVIEW
Debangshu Samanta, Gregg L Semenza
Oxidative phosphorylation enables cells to generate the large amounts of ATP required for development and maintenance of multicellular organisms. However, under conditions of reduced O2 availability, electron transport becomes less efficient, leading to increased generation of superoxide anions. Hypoxia-inducible factors switch cells from oxidative to glycolytic metabolism, to reduce mitochondrial superoxide generation, and increase the synthesis of NADPH and glutathione, in order to maintain redox homeostasis under hypoxic conditions...
May 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28623342/hif-1%C3%AE-knockdown-reduces-glycolytic-metabolism-and-induces-cell-death-of-human-synovial-fibroblasts-under-normoxic-conditions
#8
Manuel J Del Rey, Álvaro Valín, Alicia Usategui, Carmen M García-Herrero, María Sánchez-Aragó, José M Cuezva, María Galindo, Beatriz Bravo, Juan D Cañete, Francisco J Blanco, Gabriel Criado, José L Pablos
Increased glycolysis and HIF-1α activity are characteristics of cells under hypoxic or inflammatory conditions. Besides, in normal O2 environments, elevated rates of glycolysis support critical cellular mechanisms such as cell survival. The purpose of this study was to analyze the contribution of HIF-1α to the energy metabolism and survival of human synovial fibroblasts (SF) under normoxic conditions. HIF-1α was silenced using lentiviral vectors or small-interfering RNA (siRNA) duplexes. Expression analysis by qRT-PCR and western blot of known HIF-1α target genes in hypoxia demonstrated the presence of functional HIF-1α in normoxic SF and confirmed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a HIF-1α target even in normoxia...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623259/microrna-34a-encapsulated-in-hyaluronic-acid-nanoparticles-induces-epigenetic-changes-with-altered-mitochondrial-bioenergetics-and-apoptosis-in-non-small-cell-lung-cancer-cells
#9
Malav Trivedi, Amit Singh, Meghna Talekar, Grishma Pawar, Parin Shah, Mansoor Amiji
Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target only nuclear DNA. Emerging evidence suggests presence of methylation marks on mitochondrial DNA (mtDNA); but their contribution in cancer is unidentified. Expression of genes encoded on mtDNA are altered in cancer cells, along with increased glycolytic flux. Such glycolytic flux and elevated reactive oxygen species is supported by increased antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects of tumor suppressor P53, and inhibit the antioxidant response element Nrf-2, resulting in depleted glutathione levels...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622884/the-effect-of-caloric-restriction-on-the-forelimb-skeletal-muscle-fibers-of-the-hypertrophic-myostatin-null-mice
#10
Mohamed I Elashry, Antonios Matsakas, Sabine Wenisch, Stefan Arnhold, Ketan Patel
Skeletal muscle mass loss has a broad impact on body performance and physical activity. Muscle wasting occurs due to genetic mutation as in muscular dystrophy, age-related muscle loss (sarcopenia) as well as in chronic wasting disorders as in cancer cachexia. Food restriction reduces muscle mass underpinned by increased muscle protein break down. However the influence of dietary restriction on the morphometry and phenotype of forelimb muscles in a genetically modified myostatin null mice are not fully characterized...
June 13, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28622697/vitamin-c-and-doxycycline-a-synthetic-lethal-combination-therapy-targeting-metabolic-flexibility-in-cancer-stem-cells-cscs
#11
Ernestina Marianna De Francesco, Gloria Bonuccelli, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti
Here, we developed a new synthetic lethal strategy for further optimizing the eradication of cancer stem cells (CSCs). Briefly, we show that chronic treatment with the FDA-approved antibiotic Doxycycline effectively reduces cellular respiration, by targeting mitochondrial protein translation. The expression of four mitochondrial DNA encoded proteins (MT-ND3, MT-CO2, MT-ATP6 and MT-ATP8) is suppressed, by up to 35-fold. This high selection pressure metabolically synchronizes the surviving cancer cell sub-population towards a predominantly glycolytic phenotype, resulting in metabolic inflexibility...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620389/2-deoxy-d-glucose-treatment-decreases-anti-inflammatory-m2-macrophage-polarization-in-mice-with-tumor-and-allergic-airway-inflammation
#12
Qingjie Zhao, Zhulang Chu, Linnan Zhu, Tao Yang, Peng Wang, Fang Liu, Ying Huang, Fang Zhang, Xiaodong Zhang, Wenjun Ding, Yong Zhao
As important effector cells in inflammation, macrophages can be functionally polarized into either inflammatory M1 or alternatively activated anti-inflammatory M2 phenotype depending on surroundings. The key roles of glycolysis in M1 macrophage polarization have been well defined. However, the relationship between glycolysis and M2 polarized macrophages is still poorly understood. Here, we report that 2-deoxy-d-glucose (2-DG), an inhibitor of the glycolytic pathway, markedly inhibited the expressions of Arg, Ym-1, Fizz1, and CD206 molecules, the hall-markers for M2 macrophages, during macrophages were stimulated with interleukin 4...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28619994/simultaneous-stimulation-of-glycolysis-and-gluconeogenesis-by-feeding-in-the-anterior-intestine-of-the-omnivorous-gift-tilapia-oreochromis-niloticus
#13
Yong-Jun Chen, Ti-Yin Zhang, Hai-Yan Chen, Shi-Mei Lin, Li Luo, De-Shou Wang
The present study was performed to investigate the roles of anterior intestine in the postprandial glucose homeostasis of the omnivorous Genetically Improved Farmed Tilapia (GIFT). Sub-adult fish (about 173 g) were sampled at 0, 1, 3, 8 and 24 h post feeding (HPF) after 36 h of food deprivation, and the time course of changes in intestinal glucose transport, glycolysis, glycogenesis and gluconeogenesis at the transcription and enzyme activity level, as well as plasma glucose contents, were analyzed. Compared with 0 HPF (fasting for 36 h), the mRNA levels of both ATP-dependent sodium/glucose cotransporter 1 and facilitated glucose transporter 2 increased during 1-3 HPF, decreased at 8 HPF and then leveled off...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28618374/proteomic-profiling-of-german-dornfelder-grape-berries-using-data-independent-acquisition
#14
Matthias Riebel, Petra Fronk, Stefan Tenzer, Ute Distler, Heinz Decker
Grapevine is one of the most important fruit plants throughout the world. Sequencing of the grape genome in 2007 enabled in-depth analyses of the grape proteome. Whereas many studies addressed changes in proteomic composition of grapes during ripening, we focused on the proteome of mature grape berries from Dornfelder, a characteristic red wine grape for Germany. Current data-independent acquisition proteomics technology enables the analysis of proteomic compositions in a degree of accuracy that was unreachable only a few years ago...
June 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28614802/mitochondrial-dysregulation-and-glycolytic-insufficiency-functionally-impair-cd8-t-cells-infiltrating-human-renal-cell-carcinoma
#15
Peter J Siska, Kathryn E Beckermann, Frank M Mason, Gabriela Andrejeva, Allison R Greenplate, Adam B Sendor, Yun-Chen J Chiang, Armando L Corona, Lelisa F Gemta, Benjamin G Vincent, Richard C Wang, Bumki Kim, Jiyong Hong, Chiu-Lan Chen, Timothy N Bullock, Jonathan M Irish, W Kimryn Rathmell, Jeffrey C Rathmell
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28612110/differential-killing-and-radio-modifying-effects-of-iodoacetate-in-mammalian-normal-and-cancer-cells
#16
Usha Yadav, K B Anjaria, Rajesha Nairy, K B Shirsath, Utkarsha N Desai, Rajesh K Chaurasia, Nagesh N Bhat, B K Sapra
To explore possible applications of iodoacetate (IA), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; A549 (human lung carcinoma), MCF7 (human mammary cancer), a non-cancerous CHO (Chinese hamster ovary) cells and human lymphocytes. Experiments were carried out using IA concentrations ranging from 0.01 to 2.5 µg/ml, with or without (60)Coγ-radiation. In the outcomes, IA was found to exhibit higher toxicity in the cancer cells, whereas it was non-toxic/marginally toxic to the non-cancerous cells...
June 13, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28611670/identification-of-epigallocatechin-3-gallate-as-an-inhibitor-of-phosphoglycerate-mutase-1
#17
Xiaoguang Li, Shuai Tang, Qian-Qian Wang, Elaine L-H Leung, Hongyue Jin, Yongzhuo Huang, Jia Liu, Meiyu Geng, Min Huang, Shengtao Yuan, Xiao-Jun Yao, Jian Ding
Targeting metabolic enzymes is believed to provide new therapeutic opportunities for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that importantly coordinates glycolysis, pentose phosphate pathway (PPP) flux and serine biosynthesis in cancer cells and hence gains increasing interest of inhibitor discovery. Only few PGAM1 inhibitors have been reported and the molecular potency remains very limited. In an effort to discover new PGAM1 inhibitors, we carried out a biochemical assay-based screen that was focused on natural products derived small molecule compounds...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28610954/feedback-regulation-of-aldoa-activates-the-hif-1%C3%AE-mmp9-axis-to-promote-lung-cancer-progression
#18
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yu Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28608798/molecular-cloning-and-functional-characterization-of-a-hexokinase-from-the-oriental-river-prawn-macrobrachium-nipponense-in-response-to-hypoxia
#19
Shengming Sun, Fujun Xuan, Hongtuo Fu, Jian Zhu, Xianping Ge
Metabolic adjustment to hypoxia in Macrobrachium nipponense (oriental river prawn) implies a shift to anaerobic metabolism. Hexokinase (HK) is a key glycolytic enzyme in prawns. The involvement of HK in the hypoxia inducible factors (HIFs) pathway is unclear in prawns. In this study, the full-length cDNA for HK (MnHK) was obtained from M. nipponense, and its properties were characterized. The full-length cDNA (2385 bp) with an open reading frame of 1350 bp, encoded a 450-amino acid protein. MnHK contained highly conserved amino acids in the glucose, glucose-6-phosphate, ATP, and Mg(+2) binding sites...
June 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28607489/the-metabolic-function-of-cyclin-d3-cdk6-kinase-in-cancer-cell-survival
#20
Haizhen Wang, Brandon N Nicolay, Joel M Chick, Xueliang Gao, Yan Geng, Hong Ren, Hui Gao, Guizhi Yang, Juliet A Williams, Jan M Suski, Mark A Keibler, Ewa Sicinska, Ulrike Gerdemann, W Nicholas Haining, Thomas M Roberts, Kornelia Polyak, Steven P Gygi, Nicholas J Dyson, Piotr Sicinski
D-type cyclins (D1, D2 and D3) and their associated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery that drives cell proliferation. Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for patients with several cancer types, with promising results. Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2...
June 15, 2017: Nature
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