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https://www.readbyqxmd.com/read/28202415/glutamine-deprivation-sensitizes-human-breast-cancer-mda-mb-231-cells-to-trial-mediated-apoptosis
#1
Matharage Gayani Dilshara, Jin-Woo Jeong, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Ilandarage Menu Neelaka Molagoda, Seungheon Lee, Sang Rul Park, Yung Hyun Choi, Gi-Young Kim
Tumor cell metabolism is a promising target for various cancer treatments. Apart from aerobic glycolysis, cancer cell growth is dependent on glutamine (Gln) supply, leading to their survival and differentiation. Therefore, we examined whether treatment with TNF-related apoptosis-inducing ligand (TRAIL) sensitizes MDA-MB-231 cells to apoptosis under Gln deprivation condition (TRAIL/Gln deprivation). Gln deprivation decreased cell proliferation as expected, but did not induce remarkable cell death. TRAIL/Gln deprivation, however, significantly increased growth inhibition and morphological shrinkage of MDA-MB-231 cells compared to those induced by treatment with either Gln deprivation or TRAIL alone...
February 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28197395/characterization-of-the-tumor-microenvironment-and-tumor-stroma-interaction-by-non-invasive-preclinical-imaging
#2
REVIEW
Nirilanto Ramamonjisoa, Ellen Ackerstaff
Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28196867/synaptic-activity-drives-a-genomic-program-that-promotes-a-neuronal-warburg-effect
#3
Carlos Bas-Orth, Yan-Wei Tan, David Lau, Hilmar Bading
Synaptic activity drives changes in gene expression to promote long-lasting adaptations of neuronal structure and function. One example of such an adaptive response is the buildup of acquired neuroprotection, a synaptic activity- and gene transcription-mediated increase in the resistance of neurons against harmful conditions. A hallmark of acquired neuroprotection is the stabilization of mitochondrial structure and function. We therefore re-examined previously identified sets of synaptic activity-regulated genes to identify genes that are directly linked to mitochondrial function...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#4
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28184935/involvement-of-ezh2-in-aerobic-glycolysis-of-prostate-cancer-through-mir-181b-hk2-axis
#5
Tao Tao, Ming Chen, Ranran Jiang, Han Guan, Yeqing Huang, Huan Su, Qiang Hu, Xu Han, Jun Xiao
Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28183139/cancer-treatment-scheduling-and-dynamic-heterogeneity-in-social-dilemmas-of-tumour-acidity-and-vasculature
#6
Artem Kaznatcheev, Robert Vander Velde, Jacob G Scott, David Basanta
BACKGROUND: Tumours are diverse ecosystems with persistent heterogeneity in various cancer hallmarks like self-sufficiency of growth factor production for angiogenesis and reprogramming of energy metabolism for aerobic glycolysis. This heterogeneity has consequences for diagnosis, treatment and disease progression. METHODS: We introduce the double goods game to study the dynamics of these traits using evolutionary game theory. We model glycolytic acid production as a public good for all tumour cells and oxygen from vascularisation via vascular endothelial growth factor production as a club good benefiting non-glycolytic tumour cells...
February 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28177758/differential-effect-of-hypoxia-and-acidity-on-lung-cancer-cell-and-fibroblast-metabolism
#7
Alexandra Giatromanolaki, Maria Liousia, Stella Arelaki, Dimitra Kalamida, Stamatia Pouliliou, Axilleas Mitrakas, Avgi Tsolou, Efthimios Sivridis, Michael I Koukourakis
This study examined the metabolic response of lung cancer cells and normal lung fibroblasts to hypoxia and acidity. GLUT1 and HXKII mRNA/protein expression was up-regulated under hypoxia in the MRC5 fibroblasts and in the A549 and H1299 lung cancer cell lines, indicating intensified glucose absorption and glycolysis. Under hypoxia, the LDHA mRNA and LDH5 protein levels increased in the cancer cells but not in the fibroblasts. Acidity suppressed the above mentioned hypoxia effect. PDH-kinase-1 (PDK1 mRNA and protein) and inactive phosphorylated-PDH protein levels were induced under hypoxia in the cancer cells, whilst these were reduced in the MRC5 lung fibroblasts...
January 24, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28176759/snail-reprograms-glucose-metabolism-by-repressing-phosphofructokinase-pfkp-allowing-cancer-cell-survival-under-metabolic-stress
#8
Nam Hee Kim, Yong Hoon Cha, Jueun Lee, Seon-Hyeong Lee, Ji Hye Yang, Jun Seop Yun, Eunae Sandra Cho, Xianglan Zhang, Miso Nam, Nami Kim, Young-Su Yuk, So Young Cha, Yoonmi Lee, Joo Kyung Ryu, Sunghyouk Park, Jae-Ho Cheong, Sang Won Kang, Soo-Youl Kim, Geum-Sook Hwang, Jong In Yook, Hyun Sil Kim
Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28168164/vdac-tubulin-an-anti-warburg-pro-oxidant-switch
#9
REVIEW
Eduardo N Maldonado
Aerobic enhanced glycolysis characterizes the Warburg phenotype. In cancer cells, suppression of mitochondrial metabolism contributes to maintain a low ATP/ADP ratio that favors glycolysis. We propose that the voltage-dependent anion channel (VDAC) located in the mitochondrial outer membrane is a metabolic link between glycolysis and oxidative phosphorylation in the Warburg phenotype. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. Oxidation of respiratory substrates in the Krebs cycle generates NADH that enters the electron transport chain (ETC) to generate a proton motive force utilized to generate ATP and to maintain mitochondrial membrane potential (ΔΨ)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28159302/2d-dige-as-a-proteomic-biomarker-discovery-tool-in-environmental-studies-with-procambarus-clarkii
#10
Ricardo Fernández-Cisnal, Miguel A García-Sevillano, José L Gómez-Ariza, Carmen Pueyo, Juan López-Barea, Nieves Abril
: A 2D-DIGE/MS approach was used to assess protein abundance differences in the red swamp crayfish Procambarus clarkii from polluted aquatic ecosystems of Doñana National Park and surrounding areas with different pollution loads. Procambarus clarkii accumulated metals in the digestive glands and gills reflecting sediment concentrations. We first stated that, probably related to elements accumulation, pollution increased oxidative damage in P. clarkii tissues, as shown by the thiol oxidation status of proteins and MDA levels...
January 31, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28152601/quantitative-proteomics-charts-the-landscape-of-salmonella-carbon-metabolism-within-host-epithelial-cells
#11
Yanhua Liu, Kaiwen Yu, Fan Zhou, Tao Ding, Yufei Yang, Mo Hu, Xiaoyun Liu
We performed a proteomic survey of Salmonella enterica serovar Typhimurium during infection of host epithelial cells. Our data reveal substantial metabolic reshuffling of Salmonella in the host in addition to severe degeneration of bacterial flagella and chemotaxis systems. The large-scale quantitative data allowed us to chart an overview of intracellular Salmonella carbon metabolism. Notably, we found preferential utilization of glycolysis, the pentose phosphate pathway, mixed acid fermentation, and nucleotide metabolism...
February 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28151548/lack-of-appropriate-stoichiometry-strong-evidence-against-an-energetically-important-astrocyte-neuron-lactate-shuttle-in-brain
#12
REVIEW
Gerald A Dienel
Glutamate-stimulated aerobic glycolysis in astrocytes coupled with lactate shuttling to neurons where it can be oxidized was proposed as a mechanism to couple excitatory neuronal activity with glucose utilization (CMRglc ) during brain activation. From the outset, this model was not viable because it did not fulfill critical stoichiometric requirements: (i) Calculated glycolytic rates and measured lactate release rates were discordant in cultured astrocytes. (ii) Lactate oxidation requires oxygen consumption, but the oxygen-glucose index (OGI, calculated as CMRO2 /CMRglc ) fell during activation in human brain, and the small rise in CMRO2 could not fully support oxidation of lactate produced by disproportionate increases in CMRglc ...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28141873/proteomic-and-transcriptomic-study-of-brain-microvessels-in-neonatal-and-adult-mice
#13
Baptiste Porte, Clémence Chatelain, Julie Hardouin, Céline Derambure, Yasmine Zerdoumi, Michèle Hauchecorne, Nicolas Dupré, Soumeya Bekri, Bruno Gonzalez, Stéphane Marret, Pascal Cosette, Philippe Leroux
Infants born before 29 weeks gestation incur a major risk of preterm encephalopathy and subependymal/intracerebral/intraventricular haemorrhage. In mice, an ontogenic window of haemorrhage risk was recorded up to 5 days after birth in serpine1 knock-out animals. Using proteome and transcriptome approaches in mouse forebrain microvessels, we previously described the remodelling of extracellular matrix and integrins likely strengthening the vascular wall between postnatal day 5 (P5) and P10. Haemorrhage is the ultimate outcome of vessel damage (i...
2017: PloS One
https://www.readbyqxmd.com/read/28134810/acidosis-activates-endoplasmic-reticulum-stress-pathways-through-gpr4-in-human-vascular-endothelial-cells
#14
Lixue Dong, Elizabeth A Krewson, Li V Yang
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28125711/monitoring-mitochondrial-complex-i-activity-using-novel-pet-probe-18f-bcpp-ef-allows-early-detection-of-radiotherapy-effect-in-murine-squamous-cell-carcinoma
#15
Chieko Murayama, Akira T Kawaguchi, Akemi Kamijo, Katsuko Naito, Masakatsu Kanazawa, Hideo Tsukada
OBJECTIVES: Aerobic glycolysis, the main pathway of energy production in tumors (Warburg effect) allows detection of tumors by positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Since ionizing radiation (IR) is reported to switch aerobic glycolysis to mitochondrial oxidative phosphorylation, radiotherapeutic efficacy was monitored by the activity of mitochondrial complex I (MC-I), using a new PET probe 18F-BCPP-EF, 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoro-ethoxy)-ethoxy] -pyridine-3-ylmethoxy}-2H-pyridazin-3-one, compared with 18F-FDG uptake and the apoptosis index...
2017: PloS One
https://www.readbyqxmd.com/read/28122247/arginine-deprivation-inhibits-the-warburg-effect-and-upregulates-glutamine-anaplerosis-and-serine-biosynthesis-in-ass1-deficient-cancers
#16
Jeff Charles Kremer, Bethany Cheree Prudner, Sara Elaine Stubbs Lange, Gregory Richard Bean, Matthew Bailey Schultze, Caitlyn Brook Brashears, Megan DeAnna Radyk, Nathan Redlich, Shin-Cheng Tzeng, Kenjiro Kami, Laura Shelton, Aixiao Li, Zack Morgan, John Stephen Bomalaski, Takashi Tsukamoto, Jon McConathy, Loren Scott Michel, Jason Matthew Held, Brian Andrew Van Tine
Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28121054/enhanced-aerobic-glycolysis-by-s-nitrosoglutathione-via-hif-1%C3%AE-associated-glut1-aldolase-a-axis-in-human-endothelial-cells
#17
Jieping Yan, Xin Huang, Danyan Zhu, Yijia Lou
S-nitrosoglutathione (GSNO)-induced apoptosis is associated with reactive oxygen species and loss of mitochondrial Omi/HtrA2 in human endothelial cells (ECs). But its upstream regulation is still not elucidated. Here, we demonstrate that hypoxia induced factor-1α (HIF-1α)-linked aerobic glycolysis is associated with mitochondrial abnormality by treatment of human EC-derived EA.hy926 cells with GSNO (500 µM) for 6 h. GSNO exposure increased the levels of Aldolase A and glucose transporter-1 (GLUT1) mRNAs and proteins...
January 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28118603/disabled-cell-density-sensing-leads-to-dysregulated-cholesterol-synthesis-in-glioblastoma
#18
Diane M Kambach, Alan S Halim, A Gesine Cauer, Qian Sun, Carlos A Tristan, Orieta Celiku, Aparna H Kesarwala, Uma Shankavaram, Eric Batchelor, Jayne M Stommel
A hallmark of cellular transformation is the evasion of contact-dependent inhibition of growth. To find new therapeutic targets for glioblastoma, we looked for pathways that are inhibited by high cell density in astrocytes but not in glioma cells. Here we report that glioma cells have disabled the normal controls on cholesterol synthesis. At high cell density, astrocytes turn off cholesterol synthesis genes and have low cholesterol levels, but glioma cells keep this pathway on and maintain high cholesterol...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28117708/methylglyoxal-mediated-stress-correlates-with-high-metabolic-activity-and-promotes-tumor-growth-in-colorectal-cancer
#19
Barbara Chiavarina, Marie-Julie Nokin, Justine Bellier, Florence Durieux, Noëlla Bletard, Félicie Sherer, Pierre Lovinfosse, Olivier Peulen, Laurine Verset, Romain Dehon, Pieter Demetter, Andrei Turtoi, Koji Uchida, Serge Goldman, Roland Hustinx, Philippe Delvenne, Vincent Castronovo, Akeila Bellahcène
Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality...
January 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28115720/drosophila-larvae-synthesize-the-putative-oncometabolite-l-2-hydroxyglutarate-during-normal-developmental-growth
#20
Hongde Li, Geetanjali Chawla, Alexander J Hurlburt, Maria C Sterrett, Olga Zaslaver, James Cox, Jonathan A Karty, Adam P Rosebrock, Amy A Caudy, Jason M Tennessen
L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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