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Aerobic glycolysis

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https://www.readbyqxmd.com/read/28928849/glutaminase-sustains-cell-survival-via-the-regulation-of-glycolysis-and-glutaminolysis-in-colorectal-cancer
#1
Zhou Song, Bo Wei, Canrong Lu, Peiyu Li, Lin Chen
Cancer cells remodel their metabolic programs towards aerobic glycolysis and elevated glutaminolysis to meet the requirement s of rapid proliferation. Understanding how cells sense and adapt to these changes may provide new targets for therapeutic intervention. Deamination of glutamine to glutamate by glutaminase (GLS1) is an essential step in glutaminolysis. The present study revealed that the loss of GLS1 expression by RNA interference or inhibitor decreased the proliferation and viability of colorectal cancer (CRC) cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927903/linker-structure-activity-relationships-in-fluorodeoxyglucose-chlorambucil-conjugates-for-tumor-targeted-chemotherapy
#2
Mostafa El Hilali, Bastien Reux, Eric Debiton, Fernand Leal, Marie-Josephe Galmier, Magali Vivier, Jean-Michel Chezal, Elisabeth Miot-Noirault, Pascal Coudert, Valérie Weber
Nitrogen mustards, such as chlorambucil (CLB), can cause adverse side-effects due to ubiquitous distribution in non-target organs. To minimize this toxicity, strategies of tumor-targeting drug delivery have been developed, where a cytotoxic warhead is linked to a tumor-cell-specific small ligand. Malignant cells exhibit marked glucose avidity and an accelerated metabolism by aerobic glycolysis, known as the Warburg effect, and recognized as a hallmark of cancer. A targeting approach exploiting the Warburg effect by conjugation of CLB to 2-fluoro-2-deoxyglucose (FDG) was previously reported and identified two peracetylated glucoconjugates 2 and 3 with promising antitumor activities in vivo...
August 30, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28926527/genistein-suppresses-aerobic-glycolysis-and-induces-hepatocellular-carcinoma-cell-death
#3
Sainan Li, Jingjing Li, Weiqi Dai, Qinghui Zhang, Jiao Feng, Liwei Wu, Tong Liu, Qiang Yu, Shizan Xu, Wenwen Wang, Xiya Lu, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Xiaoming Fan, Wenhui Mo, Ling Xu, Chuanyong Guo
BACKGROUND: Genistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear. METHODS: Cell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation...
September 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28922425/hypoxia-inducible-factor-1-alpha-as-a-therapeutic-target-for-primary-effusion-lymphoma
#4
Prabha Shrestha, David A Davis, Ravindra P Veeranna, Robert F Carey, Coralie Viollet, Robert Yarchoan
Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma with poor prognosis caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Previous studies have revealed that HIF-1α, which mediates much of the cellular response to hypoxia, plays an important role in life cycle of KSHV. KSHV infection promotes HIF-1α activity, and several KSHV genes are in turn activated by HIF-1α. In this study, we investigated the effects of knocking down HIF-1α in PELs. We observed that HIF-1α knockdown in each of two PEL lines leads to a reduction in both aerobic and anaerobic glycolysis as well as lipid biogenesis, indicating that HIF-1α is necessary for maintaining a metabolic state optimal for growth of PEL...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28916747/hormetic-potential-of-methylglyoxal-a-side-product-of-glycolysis-in-switching-tumours-from-growth-to-death
#5
Marie-Julie Nokin, Florence Durieux, Justine Bellier, Olivier Peulen, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably favours methylglyoxal (MG) and advanced glycation end products (AGEs) formation in cancer cells. MG was initially considered a highly cytotoxic molecule with potential anti-cancer value. However, we have recently demonstrated that MG enhanced tumour growth and metastasis. In an attempt to understand this dual role, we explored MG-mediated dicarbonyl stress status in four breast and glioblastoma cancer cell lines in relation with their glycolytic phenotype and MG detoxifying capacity...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915394/overcoming-the-warburg-effect-is-it-the-key-to-survival-in-sepsis
#6
REVIEW
David Bar-Or, Matthew Carrick, Allen Tanner, Mark J Lieser, Leonard T Rael, Edward Brody
Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions)...
September 8, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28879550/new-protocol-based-on-uhplc-ms-ms-for-quantitation-of-metabolites-in-xylose-fermenting-yeasts
#7
Christiane Gonçalves Campos, Henrique César Teixeira Veras, José Antônio de Aquino Ribeiro, Patrícia Pinto Kalil Gonçalves Costa, Katiúscia Pereira Araújo, Clenilson Martins Rodrigues, João Ricardo Moreira de Almeida, Patrícia Verardi Abdelnur
Xylose fermentation is a bottleneck in second-generation ethanol production. As such, a comprehensive understanding of xylose metabolism in naturally xylose-fermenting yeasts is essential for prospection and construction of recombinant yeast strains. The objective of the current study was to establish a reliable metabolomics protocol for quantification of key metabolites of xylose catabolism pathways in yeast, and to apply this protocol to Spathaspora arborariae. Ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) was used to quantify metabolites, and afterwards, sample preparation was optimized to examine yeast intracellular metabolites...
September 6, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28876386/a-possible-relationship-between-gluconeogenesis-and-glycogen-metabolism-in-rabbits-during-myocardial-ischemia
#8
Raquel R DE Aguiar, Daniela F Vale, Renato M DA Silva, Yolanda P Muniz, Fernanda Antunes, Carlos Logullo, André L A Oliveira, Adriana J DE Almeida
Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique...
August 31, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28874730/a-comprehensive-characterization-of-the-impact-of-mycophenolic-acid-on-the-metabolism-of-jurkat-t-cells
#9
Ana A Fernández-Ramos, Catherine Marchetti-Laurent, Virginie Poindessous, Samantha Antonio, Céline Petitgas, Irène Ceballos-Picot, Pierre Laurent-Puig, Sylvie Bortoli, Marie-Anne Loriot, Nicolas Pallet
Metabolic reprogramming is critical for T cell fate and polarization and is regulated by metabolic checkpoints, including Myc, HIF-1α, AMPK and mTORC1. Our objective was to determine the impact of mycophenolic acid (MPA) in comparison with rapamycin (Rapa), an inhibitor of mTORC1, on the metabolism of Jurkat T cells. We identified a drug-specific transcriptome signature consisting of the key enzymes and transporters involved in glycolysis, glutaminolysis or nucleotide synthesis. MPA produced an early and transient drop in the intracellular ATP content related to the inhibition of de novo synthesis of purines, leading to the activation of the energy sensor AMPK...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874393/mitochondrial-topoisomerase-i-absence-enhances-aerobic-glycolysis-in-cancer
#10
Hongqiang Wang, Rui Zhou, Li Sun, Jianling Xia, Xuchun Yang, Changqie Pan, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Wangjun Liao
Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I (TOP1MT) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues...
September 5, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28859278/the-transcriptome-of-the-endometrium-and-placenta-is-associated-with-pregnancy-development-but-not-lactation-status-in-dairy-cows
#11
Stephen G Moore, Matthew S McCabe, Jacob C Green, Emily M Newsom, Matthew C Lucy
Infertility in lactating dairy cows is explained partially by the metabolic state associated with high milk production. The hypothesis was that lactating and nonlactating cows would differ in endometrial and placental transcriptomes during early pregnancy (day 28 to 42) and this difference would explain the predisposition for lactating cows to have embryonic loss at that time. Cows were either milked or not milked after calving. Reproductive [endometrium (caruncular and intercaruncular) and placenta] and liver tissues were collected on day 28, 35, and 42 of pregnancy...
July 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28841379/new-mandelalides-expand-a-macrolide-series-of-mitochondrial-inhibitors
#12
Mohamad Nazari, Jeffrey D Serrill, Xuemei Wan, Minh H Nguyen, Clemens Anklin, David A Gallegos, Amos B Smith, Jane E Ishmael, Kerry L McPhail
Mandelalides A-D (1-4) are macrocyclic polyketides known to have an unusual bioactivity profile influenced by compound glycosylation and growth phase of cultured cells. The isolation and characterization of additional natural congeners, mandelalides E-L (5-12), and the supply of synthetic compounds 1 and 12, as well as seco-mandelalide A methyl ester (13), have now facilitated mechanism of action and structure-activity relationship studies. Glycosylated mandelalides are effective inhibitors of aerobic respiration in living cells...
September 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28837697/herpesviruses-shape-tumour-microenvironment-through-exosomal-transfer-of-viral-micrornas
#13
Ohad Yogev, Stephen Henderson, Matthew John Hayes, Sara Sofia Marelli, Yifat Ofir-Birin, Neta Regev-Rudzki, Javier Herrero, Tariq Enver
Metabolic changes within the cell and its niche affect cell fate and are involved in many diseases and disorders including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KSHV latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, these miRNAs are responsible for inducing the Warburg effect in infected cells. Here we identify a novel mechanism enabling KSHV to manipulate the metabolic nature of the tumour microenvironment...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28830930/increased-heme-synthesis-in-yeast-induces-a-metabolic-switch-from-fermentation-to-respiration-even-under-conditions-of-glucose-repression
#14
Tiantian Zhang, Pengli Bu, Joey Zeng, Ales Vancura
Regulation of mitochondrial biogenesis and respiration is a complex process that involves several signaling pathways and transcription factors, as well as communication between the nuclear and mitochondrial genomes. Under aerobic condition, the budding yeast Saccharomyces cerevisiae metabolizes glucose predominantly by glycolysis and fermentation. We have recently shown that altered chromatin structure in yeast induces respiration by a mechanism that requires transport and metabolism of pyruvate in mitochondria...
August 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28827059/enhanced-aerobic-glycolysis-of-nasopharyngeal-carcinoma-cells-by-epstein-barr-virus-latent-membrane-protein-1
#15
Wei-Wen Sung, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells...
August 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#16
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28821788/bioenergetic-adaptations-in-chemoresistant-ovarian-cancer-cells
#17
Sajad Dar, Jasdeep Chhina, Ismail Mert, Dhananjay Chitale, Thomas Buekers, Hareena Kaur, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan
Earlier investigations have revealed that tumor cells undergo metabolic reprogramming and mainly derive their cellular energy from aerobic glycolysis rather than oxidative phosphorylation even in the presence of oxygen. However, recent studies have shown that certain cancer cells display increased oxidative phosphorylation or high metabolically active phenotype. Cellular bioenergetic profiling of 13 established and 12 patient derived ovarian cancer cell lines revealed significant bioenergetics diversity. The bioenergetics phenotype of ovarian cancer cell lines correlated with functional phenotypes of doubling time and oxidative stress...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819926/targeting-metabolic-pathways-for-head-and-neck-cancers-therapeutics
#18
Masashi Yamamoto, Hidenori Inohara, Takashi Nakagawa
Cancer cells have distinctive energy metabolism pathways that support their rapid cell division. The preference for anaerobic glycolysis under the normal oxygen condition is known as the Warburg effect and has been observed in head and neck cancers. These metabolic changes are controlled by cancer-related transcription factors, such as tumor suppressor gene and hypoxia inducible factor 1α. In addition, various metabolic enzymes also actively regulate cancer-specific metabolism including the switch between aerobic and anaerobic glycolysis...
August 17, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28818664/lactate-dehydrogenase-a-is-indispensable-for-vascular-smooth-muscle-cell-proliferation-and-migration
#19
Ji-Hyun Kim, Kwi-Hyun Bae, Jun-Kyu Byun, Sungwoo Lee, Jung-Guk Kim, In Kyu Lee, Gwon-Soo Jung, You Mie Lee, Keun-Gyu Park
The proliferation and migration of vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of atherosclerosis. Increased aerobic glycolysis is a key feature of cellular phenotypes including cancer and immune cells. However, the role of aerobic glycolysis in the atherogenic phenotype of VSMCs remains largely unknown. Here, we investigated the role of lactate dehydrogenase-A (LDHA), which is a key enzyme for glycolysis, in the proliferation and migration of VSMCs. Activation of primary rat VSMCs with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF) increased their proliferation and migration, glycolytic activity, and expression of LDHA...
August 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#20
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing Mucin 1 (MUC1) rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrates that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation was accompanied by a relative decrease in the proliferation of MUC1-overexpressing cells compared with steady-state conditions...
August 30, 2017: Journal of Proteome Research
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