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Aerobic glycolysis

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https://www.readbyqxmd.com/read/29139328/repression-of-oxidative-phosphorylation-sensitizes-leukemia-cell-lines-to-cytarabine
#1
Burcu Yucel, Mehmet Sonmez
OBJECTIVES: Leukemia is a group of bone marrow cancers and drug resistance is one of the challenges in treatment. Caffeic acid phenethyl ester's (CAPE's) anti-proliferative and apoptotic properties have been reported in leukemia cell lines. However, CAPE's effect on drug resistance and cellular metabolism is still unknown. Thus, in this study, we aimed to explore CAPE's effect on drug resistance and oxidative phosphorylation (oxphos). METHODS: Leukemia cell lines NB-4, HL-60, and K562 were treated with CAPE...
November 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29137422/pkm2-can-enhance-pluripotency-in-escs-and-promote-somatic-cell-reprogramming-to-ipscs
#2
Shengtang Qin, Danli Yang, Kang Chen, Haolan Li, Liqiang Zhang, Yuan Li, Rongrong Le, Xiaojie Li, Shaorong Gao, Lan Kang
Aerobic glycolysis is one of the most important common characteristics in both cancer cells and stem cells. Metabolism switch has been discovered as an important early event in the process of reprogramming somatic cells to induced pluripotent stem cells (iPSCs). As a rate limiting kinase in glycolysis, Pkm2 has been reported playing critical roles in many tumors, yet its role in stem cells and iPSCs induction is poorly defined. In the present study, we showed that Pkm2 is a predominant pyruvate kinase in embryonic stem cells (ESCs), and its expression increases many pluripotent genes...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137386/mitochondrial-calcium-uniporter-as-a-target-of-microrna-340-and-promoter-of-metastasis-via-enhancing-the-warburg-effect
#3
Changhui Yu, Yuhao Wang, Jiawen Peng, Qiang Shen, Mimi Chen, Wei Tang, Xiumei Li, Chunqing Cai, Bin Wang, Shaoxi Cai, Xiaojing Meng, Fei Zou
Background: A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca(2+) uptake into mitochondria, was found to promote cancer progression and metastasis. However, its explicit role in shifting metabolism of breast cancer cells has not been defined. Methods: We evaluated MCU overexpression or knock-down on migration, invasion and glucose metabolismin breast cancer cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137232/integration-of-metabolomics-transcriptomics-and-microrna-expression-profiling-reveals-a-mir-143-hk2-glucose-network-underlying-zinc-deficiency-associated-esophageal-neoplasia
#4
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...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129024/metabolic-regulation-of-the-ccn-family-genes-by-glycolysis-in-chondrocytes
#5
Sho Akashi, Takashi Nishida, Abdellatif El-Seoudi, Masaharu Takigawa, Seiji Iida, Satoshi Kubota
The CCN family consists of 6 genes in the mammalian genome and produces multifunctional proteins involved in a variety of biological processes. Recent reports indicate the profound roles of CCN2 in energy metabolism in chondrocytes, and Ccn2 deficiency is known to alter the expression of 2 other family members including Ccn3. However, almost nothing is known concerning the regulation of the CCN family genes by energy metabolism. In order to gain insight into this critical issue, we initially and comprehensively evaluated the effect of inhibition of glycolysis on the expression of all of the CCN family genes in chondrocytic cells...
November 11, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29128957/expression-of-glut-1-in-malignant-melanoma-and-melanocytic-nevi-an-immunohistochemical-study-of-400-cases
#6
Miroslav Důra, Kristýna Němejcová, Radek Jakša, Michaela Bártů, Ondřej Kodet, Ivana Tichá, Romana Michálková, Pavel Dundr
The glucose transporter-1 (Glut-1) is a cell membrane glycoprotein involved in glucose uptake. An increased expression of Glut-1 is an important cell adaptation mechanism against hypoxia. An upregulation of Glut-1 can be found in several types of malignant tumors, which are able to reprogram their metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect). However, the data regarding melanocytic lesions is equivocal. We performed comprehensive immunohistochemical analysis of the Glut-1 expression in 225 malignant melanomas (MM) and 175 benign nevi...
November 11, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29119048/elucidating-immunometabolic-targets-in-glioblastoma
#7
REVIEW
Pooja Agarwal, Michael J Pajor, David M Anson, Maheedhara R Guda, Collin M Labak, Andrew J Tsung, Kiran K Velpula
Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29117556/cdk8-kinase-activity-promotes-glycolysis
#8
Matthew D Galbraith, Zdenek Andrysik, Ahwan Pandey, Maria Hoh, Elizabeth A Bonner, Amanda A Hill, Kelly D Sullivan, Joaquín M Espinosa
Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancerous tissues. Despite its importance in cancer development, our understanding of mechanisms driving this form of metabolic reprogramming is incomplete. We report here an analysis of colorectal cancer cells engineered to carry a single point mutation in the active site of the Mediator-associated kinase CDK8, creating hypomorphic alleles sensitive to bulky ATP analogs. Transcriptome analysis revealed that CDK8 kinase activity is required for the expression of many components of the glycolytic cascade...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29114996/impaired-p53-cep-1-is-associated-with-lifespan-extension-through-an-age-related-imbalance-in-the-energy-metabolism-of-c-%C3%A2-elegans
#9
Sumino Yanase, Hitoshi Suda, Kayo Yasuda, Naoaki Ishii
In the nematode Caenorhabditis elegans, the mammalian tumor suppressor p53 ortholog CEP-1 mediates the stress response, activates germ line apoptosis and regulates meiotic chromosome segregation. A reduction in its expression, which frequently occurs in mammalian cancer cells, extends lifespan and induces an adaptive response in C. elegans. However, these effects do not involve an increase in oxidative stress resistance. Here, we showed that intermittent exposure to hyperoxia, which induces oxidative stress resistance and lowers the production of ROS derived from mitochondrial respiration in C...
November 8, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29114403/transcriptomic-analysis-of-aerobic-respiratory-and-anaerobic-photosynthetic-states-in-rhodobacter-capsulatus-and-their-modulation-by-global-redox-regulators-rega-fnrl-and-crtj
#10
Joseph E Kumka, Heidi Schindel, Mingxu Fang, Sebastien Zappa, Carl E Bauer
Anoxygenicphotosynthetic prokaryotes have simplified photosystems that represent ancient lineages that predate the more complex oxygen evolving photosystems present in cyanobacteria and chloroplasts. These organisms thrive under illuminated anaerobic photosynthetic conditions, but also have the ability to grow under dark aerobic respiratory conditions. This study provides a detailed snapshot of transcription ground states of both dark aerobic and anaerobic photosynthetic growth modes in the purple photosynthetic bacterium Rhodobactercapsulatus...
September 2017: Microbial Genomics
https://www.readbyqxmd.com/read/29114069/bag3-directly-stabilizes-hexokinase-2-mrna-and-promotes-aerobic-glycolysis-in-pancreatic-cancer-cells
#11
Ming-Xin An, Si Li, Han-Bing Yao, Chao Li, Jia-Mei Wang, Jia Sun, Xin-Yu Li, Xiao-Na Meng, Hua-Qin Wang
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29113698/the-control-of-oligodendrocyte-bioenergetics-by-interferon-gamma-ifn-%C3%AE-and-src-homology-region-2-domain-containing-phosphatase-1-shp-1
#12
Scott B Minchenberg, Paul T Massa
Glycolysis and mitochondrial respiration are essential for oligodendrocyte metabolism in both the developing and adult CNS. Based on recent reports on the effects of the proinflammatory cytokine IFN-γ on metabolism and on oligodendrocytes, we addressed whether IFN-γ may affect oligodendrocyte bioenergetics in ways relevant to CNS disease. Oligodendrocytes of mice treated with IFN-γ showed significant reductions in aerobic glycolysis and mitochondrial respiration. As expected, IFN-γ treatment led to the induction of STAT1 in oligodendrocytes indicating active signaling into these cells...
October 28, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29109698/the-emerging-facets-of-non-cancerous-warburg-effect
#13
Alyaa M Abdel-Haleem, Nathan E Lewis, Neema Jamshidi, Katsuhiko Mineta, Xin Gao, Takashi Gojobori
The Warburg effect (WE), or aerobic glycolysis, is commonly recognized as a hallmark of cancer and has been extensively studied for potential anti-cancer therapeutics development. Beyond cancer, the WE plays an important role in many other cell types involved in immunity, angiogenesis, pluripotency, and infection by pathogens (e.g., malaria). Here, we review the WE in non-cancerous context as a "hallmark of rapid proliferation." We observe that the WE operates in rapidly dividing cells in normal and pathological states that are triggered by internal and external cues...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29109024/ampk-regulates-immunometabolism-in-sepsis
#14
Jun Huang, Ke Liu, Shan Zhu, Min Xie, Rui Kang, Lizhi Cao, Daolin Tang
Sepsis and septic shock remain challenging for intensive care units worldwide and have limited treatment options; therefore, identification of targetable key players in systemic inflammation and multiple organ failure is urgently needed. Here, we show that AMP-activated protein kinase (AMPK) is a negative regulator of bioenergetic reprogramming in immune cells and suppresses sepsis development in vivo. Mechanistically, AMPK deficiency increases pyruvate kinase isozyme M2 (PKM2)-dependent aerobic glycolysis, which leads to the release of high mobility group box 1 (HMGB1, a late mediator of lethal systemic inflammation) in macrophages and monocytes...
November 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29100699/glucose-starvation-impairs-dna-repair-in-tumour-cells-selectively-by-blocking-histone-acetylation
#15
Rena Ampferl, Hans Peter Rodemann, Claus Mayer, Tobias Tim Alexander Höfling, Klaus Dittmann
BACKGROUND AND PURPOSE: Tumour cells are characterized by aerobic glycolysis and thus have high glucose consumption. Because repairing radiation-induced DNA damage is an energy-demanding process, we hypothesized that glucose starvation combined with radiotherapy could be an effective strategy to selectively target tumour cells. MATERIAL AND METHODS: We glucose-starved tumour cells (A549, FaDu) in vitro and analysed their radiation-induced cell responses compared to normal fibroblasts (HSF7)...
October 31, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29094170/mir-361-5p-modulates-metabolism-and-autophagy-via-the-sp1-mediated-regulation-of-pkm2-in-prostate-cancer
#16
Zhixin Ling, Dachuang Liu, Guangyuan Zhang, Qing Liang, Ping Xiang, Yan Xu, Conghui Han, Tao Tao
Prostate cancer (PCa) is a leading cause of death among men. The dysregulation of metabolism and autophagy contributes to the progression of PCa. The transcription factor specificity protein 1 (Sp1) is implicated in the regulation of metabolism and autophagy. We confirmed that Sp1 is overexpressed in castration-resistant prostate cancer (CRPC) cells. However, the roles of Sp1 in PCa metabolism and autophagy remain unclear. Thus, in the present study, we retrieved the GSE35988 dataset from Gene Expression Omnibus (GEO) database to reinvestigate Sp1 expression and its role in PCa...
September 2017: Oncology Reports
https://www.readbyqxmd.com/read/29093638/inhibition-of-hif1%C3%AE-and-pdk-induces-cell-death-of-glioblastoma-multiforme
#17
Jiwon Esther Han, Pyung Won Lim, Chul Min Na, You Sik Choi, Joo Young Lee, Yona Kim, Hyung Woo Park, Hyo Eun Moon, Man Seung Heo, Hye Ran Park, Dong Gyu Kim, Sun Ha Paek
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia...
October 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29070571/lithium-induces-aerobic-glycolysis-and-glutaminolysis-in-collecting-duct-principal-cells
#18
Mohammad Alsady, Theun de Groot, Marleen Louise Adriënne Kortenoeven, Claudia Carmone, Kim Neijman, Melissa Bekkenkamp-Grovenstein, Udo Engelke, Ron Wevers, Ruben Baumgarten, Ron Korstanje, Peter M T Deen
Lithium, given to bipolar disorder patients, causes nephrogenic diabetes insipidus (Li-NDI), a urinary concentrating defect. Li-NDI is due to downregulation of principal cell AQP2 expression, which coincides with principal cell proliferation. The metabolic effect of lithium on principal cells, however, is unknown and investigated here. Earlier, we have shown that the carbonic anhydrase (CA) inhibitor acetazolamide attenuated Li-induced downregulation in mouse collecting duct (mpkCCD) cells. Of the eight CAs present in mpkCCD cells, siRNA and drug treatments showed that downregulation of CA9 and to some extent CA12 attenuated Li-induced AQP2 downregulation...
October 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29069720/reduced-production-and-uptake-of-lactate-are-essential-for-the-ability-of-wnt5a-signaling-to-inhibit-breast-cancer-cell-migration-and-invasion
#19
Chandra Prakash Prasad, Katja Södergren, Tommy Andersson
Here we investigated the impact of WNT5A signaling on aerobic glycolysis and evaluated its effects on breast cancer cell migration/invasion. WNT5A signaling reduced migration and lactate production and caused selective down-regulation of the glycolytic enzyme phosphofructokinase platelet-type (PFKP). These events occurred in parallel with a WNT5A-induced inhibition of β-catenin signaling. Support for essential involvement of β-catenin and PFKP in lactate production and migration/invasion was obtained by siRNA knockdown of their expression...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058718/pkm2-methylation-by-carm1-activates-aerobic-glycolysis-to-promote-tumorigenesis
#20
Fabao Liu, Fengfei Ma, Yuyuan Wang, Ling Hao, Hao Zeng, Chenxi Jia, Yidan Wang, Peng Liu, Irene M Ong, Baobin Li, Guojun Chen, Jiaoyang Jiang, Shaoqin Gong, Lingjun Li, Wei Xu
Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked...
November 2017: Nature Cell Biology
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