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Metabolic reprogramming

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https://www.readbyqxmd.com/read/28641785/acute-detachment-of-hexokinase-ii-from-mitochondria-modestly-increases-oxygen-consumption-of-the-intact-mouse-heart
#1
Rianne Nederlof, Simone Denis, Benjamin Lauzier, Christine Des Rosiers, Markku Laakso, Jacob Hagen, Carmen Argmann, Ronald Wanders, Riekelt H Houtkooper, Markus W Hollmann, Sander M Houten, Coert J Zuurbier
OBJECTIVE: Cardiac hexokinase II (HKII) can translocate between cytosol and mitochondria and change its cellular expression with pathologies such as ischemia-reperfusion, diabetes and heart failure. The cardiac metabolic consequences of these changes are unknown. Here we measured energy substrate utilization in cytosol and mitochondria using stabile isotopes and oxygen consumption of the intact perfused heart for 1) an acute decrease in mitochondrial HKII (mtHKII), and 2) a chronic decrease in total cellular HKII...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28641473/co-targeting-intracellular-ph-and-essential-amino-acid-uptake-cooperates-to-induce-cell-death-of-t-all-ll-cells
#2
Véronique Imbert, Marielle Nebout, Didier Mary, Hitoshi Endou, Michael F Wempe, Claudiu T Supuran, Jean-Yves Winum, Jean-François Peyron
Cancer cells reprogram their metabolism to optimize their growth and proliferation in the host microenvironment. For this purpose, they enhance the uptake of extracellular nutrients and deal with the metabolic waste products through the overexpression of numerous membrane proteins including amino-acid transporters (LAT1) and acid-base regulating enzymes, such as carbonic anhydrases (CAs). Here we describe the anti-tumoral effects of a new class of CAXII inhibitors, the glycosyl coumarins on T-ALL/LL cells. These effects appeared to be mediated through inhibition of mTOR/Akt pathway and c-myc downregulation...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28640191/phenotypic-plasticity-and-cell-fate-decisions-in-cancer-insights-from-dynamical-systems-theory
#3
REVIEW
Dongya Jia, Mohit Kumar Jolly, Prakash Kulkarni, Herbert Levine
Waddington's epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of "landscape" in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an "attractor" that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes...
June 22, 2017: Cancers
https://www.readbyqxmd.com/read/28637872/hydrogen-sulfide-modulates-eukaryotic-translation-initiation-factor-2%C3%AE-eif2%C3%AE-phosphorylation-status-in-the-integrated-stress-response-pathway
#4
Vinita Yadav, Xing-Huang Gao, Belinda Willard, Maria Hatzoglou, Ruma Banerjee, Omer Kabil
Hydrogen sulfide (H2S) regulates various physiological processes including neuronal activity, vascular tone, inflammation, and energy metabolism. Moreover, H2S elicits cytoprotective effects against stressors in various cellular models of injury. However, the mechanism of the signaling pathways mediating the cytoprotective functions of H2S is not well understood. We previously uncovered a heme-dependent metabolic switch for transient induction of H2S production in the transsulfuration pathway. Here, we demonstrate that increased endogenous H2S production or its exogenous administration modulates major components of the integrated stress response (ISR) promoting a metabolic state primed for stress response...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#5
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28636890/memory-t-cells-a-helpful-guard-for-allogeneic-hematopoietic-stem-cell-transplantation-without-causing-graft-versus-host-disease
#6
REVIEW
Wei Huang, Nelson J Chao
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT) and the major cause of nonrelapse morbidity and mortality of AHSCT. In AHSCT, donor T cells facilitate hematopoietic stem cell (HSC) engraftment, contribute to anti-infection immunity, and mediate graft-versus-leukemia (GVL) responses. However, activated alloreactive T cells also attack recipient cells in vital organs, leading to GVHD. Different T-cell subsets, including naïve T (TN) cells, memory T (TM) cells, and regulatory T (Treg) cells mediate different forms of GVHD and GVL; TN cells mediate severe GVHD, whereas TM cells do not cause GVHD, but preserve T-cell function including GVL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28630930/real-time-quantitative-analysis-of-metabolic-flux-in-live-cells-using-a-hyperpolarized-micromagnetic-resonance-spectrometer
#7
Sangmoo Jeong, Roozbeh Eskandari, Sun Mi Park, Julio Alvarez, Sui Seng Tee, Ralph Weissleder, Michael G Kharas, Hakho Lee, Kayvan R Keshari
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28627410/current-and-upcoming-mitochondrial-targets-for-cancer-therapy
#8
REVIEW
Hyoung Kyu Kim, Yeon Hee Noh, Bernd Nilius, Kyung Soo Ko, Byoung Doo Rhee, Nari Kim, Jin Han
Mitochondria are essential intracellular organelles that regulate energy metabolism, cell death, and signaling pathways that are important for cell proliferation and differentiation. Therefore, mitochondria are fundamentally implicated in cancer biology, including initiation, growth, metastasis, relapse, and acquired drug resistance. Based on these implications, mitochondria have been proposed as a major therapeutic target for cancer treatment. In addition to classical view of mitochondria in cancer biology, recent studies found novel pathophysiological roles of mitochondria in cancer...
June 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#9
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28626065/metabolic-reprogramming-commits-differentiation-of-human-cd27-igd-b-cells-to-plasmablasts-or-cd27-igd-cells
#10
Masataka Torigoe, Shigeru Iwata, Shingo Nakayamada, Kei Sakata, Mingzeng Zhang, Maiko Hajime, Yusuke Miyazaki, Manabu Narisawa, Koji Ishii, Hirotaka Shibata, Yoshiya Tanaka
B cells play a crucial role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). However, the relevance of the metabolic pathway in the differentiation of human B cell subsets remains unknown. In this article, we show that the combination of CpG/TLR9 and IFN-α markedly induced the differentiation of CD27(+)IgD(+) unswitched memory B cells into CD27(hi)CD38(hi) plasmablasts. The response was accompanied by mammalian target of rapamycin complex 1 (mTORC1) activation and increased lactate production, indicating a shift to glycolysis...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28624784/mitochondrial-pyruvate-carrier-function-determines-cell-stemness-and-metabolic-reprogramming-in-cancer-cells
#11
Xiaoli Li, Gaoyang Han, Xiaoran Li, Quancheng Kan, Zhirui Fan, Yaqing Li, Yasai Ji, Jing Zhao, Mingzhi Zhang, Mantas Grigalavicius, Viktor Berge, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo
One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623714/can-the-co-dependence-of-the-immune-system-and-angiogenesis-facilitate-pharmacological-targeting-of-tumours
#12
REVIEW
Lorenzo Mortara, Andrew V Benest, David O Bates, Douglas M Noonan
Tumours elicit a number of mechanisms to induce a reprogramming of innate and adaptive immune cells to their advantage, inducing a pro-angiogenic phenotype. Investigation of these events is now leading to the identification of specific myeloid and lymphoid cell-targeted therapies, as well as of unexplored off-target activities of clinically relevant chemotherapeutic and metabolic drugs. It is also leading to an enhanced understanding of the interplay between angiogenesis and the immune system, and the value of novel co-targeting approaches using both immunotherapy and anti-angiogenic therapy...
June 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28623298/constraint-based-modeling-identifies-new-putative-targets-to-fight-colistin-resistant-a-baumannii-infections
#13
Luana Presta, Emanuele Bosi, Leila Mansouri, Lenie Dijkshoorn, Renato Fani, Marco Fondi
Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622688/integration-of-metabolomics-transcriptomics-and-microrna-expression-profiling-reveals-a-mir-143-hk2-glucose-network-underlying-zinc-deficiency-associated-esophageal-neoplasia
#14
Louise Y Fong, Ruiyan Jing, Karl J Smalley, Cristian Taccioli, Johannes Fahrmann, Dinesh K Barupal, Hansjuerg Alder, John L Farber, Oliver Fiehn, Carlo M Croce
Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#15
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28621843/metabolic-reprogramming-in-the-tumour-microenvironment-a-hallmark-shared-by-cancer-cells-and-t-lymphocytes
#16
REVIEW
Katrina E Allison, Brenda L Coomber, Byram W Bridle
Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and upregulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system...
June 16, 2017: Immunology
https://www.readbyqxmd.com/read/28620452/metabolic-reprogramming-during-the-trypanosoma-brucei-life-cycle
#17
REVIEW
Terry K Smith, Frédéric Bringaud, Derek P Nolan, Luisa M Figueiredo
Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites...
2017: F1000Research
https://www.readbyqxmd.com/read/28619042/metabolic-targeting-of-hif-dependent-glycolysis-reduces-lactate-increases-oxygen-consumption-and-enhances-response-to-high-dose-single-fraction-radiotherapy-in-hypoxic-solid-tumors
#18
Eric Leung, Rob A Cairns, Naz Chaudary, Ravi N Vellanki, Tuula Kalliomaki, Eduardo H Moriyama, Hilda Mujcic, Brian C Wilson, Bradly G Wouters, Richard Hill, Michael Milosevic
BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28616987/impact-of-low-intensity-pulsed-ultrasound-on-transcript-and-metabolite-abundance-in-saccharomyces-cerevisiae
#19
Michael C Schultz, Jian Zhang, Xian Luo, Oleksandra Savchenko, Liang Li, Michael Deyholos, Jie Chen
The interactions of ultrasound with biological materials are exploited for diagnostic, interventional and therapeutic multiple applications in medicine and can improve biological productivity in industrial biotechnological applications, such as biofuel generation, vaccine and antibodies production. Accordingly, there is great interest in better understanding the biological effects of ultrasound. In this paper, we studied the impact of low-intensity pulsed ultrasound (LIPUS) on RNA expression and metabolism of S...
June 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28615919/sequence-analysis-and-phylogenetic-studies-of-hypoxia-inducible-factor-1%C3%AE
#20
Jagadeesha Poyya, Chandrashekhar G Joshi, D Jagadeesha Kumar, H G Nagendra
Hypoxia-inducible factors (HIF) belong to the basic helix loop helix-PER ARNT SIM (bHLH-PAS) family of transcription factors that induce metabolic reprogramming under hypoxic condition. The phylogenetic studies of hypoxia-inducible factor-1α (HIF-1α) sequences across different organisms/species may leave a clue on the evolutionary relationships and its probable correlation to tumorigenesis and adaptation to low oxygen environments. In this study, we have aimed at the evolutionary investigation of the protein HIF-1α across different species to decipher their sequence variations/mutations and look into the probable causes and abnormal behaviour of this molecule under exotic conditions...
2017: Cancer Informatics
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