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Aerobic glycolysis

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https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13c-lactate
#1
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials and this study investigates the effect of MK2206, a non-ATP competitive inhibitor, on the cellular metabolism in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes (e...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29317521/ca2-dependent-demethylation-of-phosphatase-pp2ac-promotes-glucose-deprivation-induced-cell-death-independently-of-inhibiting-glycolysis
#2
Ha Yin Lee, Yoko Itahana, Stefan Schuechner, Masahiro Fukuda, H Shawn Je, Egon Ogris, David M Virshup, Koji Itahana
Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1...
January 9, 2018: Science Signaling
https://www.readbyqxmd.com/read/29305935/hedgehog-yap-signaling-pathway-regulates-glutaminolysis-to-control-hepatic-stellate-cell-activation
#3
Kuo Du, Jeongeun Hyun, Richard T Premont, Steve S Choi, Gregory A Michelotti, Marzena Swiderska-Syn, George D Dalton, Eric Thelen, Bahar Salimian Rizi, Youngmi Jung, Anna Mae Diehl
BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes-associated protein 1 (YAP1 or YAP) and inducing aerobic glycolysis. However, increased aerobic glycolysis alone cannot meet the high metabolic demands of myofibroblastic HSCs. Determining the metabolic processes of these cells could lead to strategies to prevent progressive liver fibrosis, so we investigated whether glutaminolysis (conversion of glutamine to alpha-ketoglutarate) sustains energy metabolism and permits anabolism when Q-HSCs become myofibroblastic, and whether this is controlled by hedgehog signaling to YAP...
January 3, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29303786/aerobic-glycolysis-in-amyotrophic-lateral-sclerosis-and-huntington-s-disease
#4
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Neurodegenerative cells are the sites of numerous metabolic and energetic abnormalities with abnormalities in energy production. Energy is the primary determinant of neuronal viability. In neurodegenerative cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), WNT/β-catenin pathway is upregulated. We focused this review on the hypothesis of aerobic glycolysis stimulated by the upregulation of WNT/β-catenin pathway in ALS and HD...
January 5, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29301575/warburg-effect-hypothesis-in-autism-spectrum-disorders
#5
REVIEW
Alexandre Vallée, Jean-Noël Vallée
Autism spectrum disorder (ASD) is a neurodevelopmental disease which is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. In altered cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In ASD, the canonical WNT/β-catenin pathway is upregulated. We focus this review on the hypothesis of Warburg effect stimulated by the overexpression of the canonical WNT/β-catenin pathway in ASD. Upregulation of WNT/β-catenin pathway induces aerobic glycolysis, named Warburg effect, through activation of glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactate dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH)...
January 4, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29299177/pkm2-in-carcinogenesis-and-oncotherapy
#6
REVIEW
Xia He, Suya Du, Tiantian Lei, Xiang Li, Yilong Liu, Hailian Wang, Rongsheng Tong, Yi Wang
Tumor cell metabolism is characterized by abundant glucose consumption and aerobic glycolysis. And pyruvate kinase M2 (PKM2) plays a decisive role in glycolysis, significantly contributing to the Warburg effect, tumor growth, angiogenesis, cell division, metastasis and apoptosis. To date, researchers have unraveled the potential of pyruvate kinase M2 as an antitumor target, which suggests a new orientation for oncotherapy. Herein, we focus on the role of pyruvate kinase M2 in tumor cell development and its function as a potential new therapeutic target for tumor treatment...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29299159/lactate-activated-macrophages-induced-aerobic-glycolysis-and-epithelial-mesenchymal-transition-in-breast-cancer-by-regulation-of-ccl5-ccr5-axis-a-positive-metabolic-feedback-loop
#7
Sensen Lin, Li Sun, Xiaodan Lyu, Xiongfei Ai, Danyu Du, Nan Su, Hongyang Li, Luyong Zhang, Jun Yu, Shengtao Yuan
Aberrant energy metabolism is critical for cancer progression. Tumor-associated macrophages (TAMs) can stimulate tumor angiogenesis and enhance cancer metastasis; however, the metabolic interaction between cancer cells and macrophages characterized by lactate shuttles remains unclear. Here, we showed that lactate activated human macrophages to a TAM-like phenotype and stimulated the secretion of CCL5 by activation of Notch signaling in macrophages. Reciprocally, CCL5 increased cell migration, induced cancer cell EMT, and promoted aerobic glycolysis in breast cancer cells, suggesting a positive metabolic feedback loop in the co-culture system...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296215/cell-surface-grp78-promotes-tumor-cell-histone-acetylation-through-metabolic-reprogramming-a-mechanism-which-modulates-the-warburg-effect
#8
Udhayakumar Gopal, Salvatore V Pizzo
Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2-Macroglobulin (α2M*) signals through tumor Cell Surface GRP78 (CS-GRP78) to regulate tumor cell proliferation through multiple signaling pathway. Here, we demonstrate that the α2M*/CS-GRP78 axis regulates acetyl-CoA synthesis and thus functions as an epigenetic modulator by enhancing histone acetylation in cancer cells...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29291405/enhanced-glycometabolism-as-a-mechanism-of-nqo1-potentiated-growth-of-nsclc-revealed-by-metabolomic-profiling
#9
Xuefang Cheng, Fang Liu, Huiying Liu, Guangji Wang, Haiping Hao
NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, has been considered as a potential poor prognostic biomarker and a promising therapeutic target for patients with non-small cell lung cancer (NSCLC) due to its frequent overexpression and significantly increased activity in NSCLC. Previous studies have shown that depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. However, the underlying mechanisms whereby NQO1 potentiates proliferation have not been fully understood...
December 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29290953/viral-e6-e7-oncogene-and-cellular-hexokinase-2-expression-in-hpv-positive-cancer-cell-lines
#10
Karin Hoppe-Seyler, Anja Honegger, Felicitas Bossler, Jasmin Sponagel, Julia Bulkescher, Claudia Lohrey, Felix Hoppe-Seyler
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. Cancer cells typically exhibit metabolic alterations which support their malignant growth. These include an enhanced rate of aerobic glycolysis ('Warburg effect') which in cancer cells is often linked to an increased expression of the rate-limiting glycolytic enzyme Hexokinase 2 (HK2). Intriguingly, recent studies indicate that the HPV E6/E7 oncogenes cause the metabolic reprogramming in HPV-positive cancer cells by directly upregulating HK2 expression...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289511/opening-of-voltage-dependent-anion-channels-promotes-reactive-oxygen-species-generation-mitochondrial-dysfunction-and-cell-death-in-cancer-cells
#11
David N DeHart, Diana Fang, Kareem Heslop, Li Li, John J Lemasters, Eduardo N Maldonado
Enhancement of aerobic glycolysis and suppression of mitochondrial metabolism characterize the pro-proliferative Warburg phenotype of cancer cells. High free tubulin in cancer cells closes voltage dependent anion channels (VDAC) to decrease mitochondrial membrane potential (ΔΨ), an effect antagonized by erastin, the canonical promotor of ferroptosis. Previously, we identified six compounds (X1-X6) that also block tubulin-dependent mitochondrial depolarization. Here, we hypothesized that VDAC opening after erastin and X1-X6 increases mitochondrial metabolism and reactive oxygen species (ROS) formation, leading to ROS-dependent mitochondrial dysfunction, bioenergetic failure and cell death...
December 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29288934/microplastics-have-a-more-profound-impact-than-elevated-temperatures-on-the-predatory-performance-digestion-and-energy-metabolism-of-an-amazonian-cichlid
#12
Bin Wen, Nan Zhang, Shi-Rong Jin, Zai-Zhong Chen, Jian-Zhong Gao, Ying Liu, Han-Peng Liu, Zhe Xu
Knowledge on the impacts of microplastics (MPs) pollution on freshwater environments and biota remains limited. Meanwhile, freshwater ecosystems have been threatened by elevated temperatures caused by climate change. To date, no information exists on how MPs-especially under elevated temperature conditions-affect predatory performance, digestive processes and metabolic pathways in freshwater organisms. Here, we examined MPs, elevated temperature and their combined effects on juveniles (0+ group) of an Amazonian cichlid, the discus fish (Symphysodon aequifasciatus)...
December 26, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29288205/extracellular-lactate-a-novel-measure-of-t-cell-proliferation
#13
James T Grist, Lorna B Jarvis, Zoya Georgieva, Sara Thompson, Harpreet Kaur Sandhu, Keith Burling, Ashley Clarke, Sarah Jackson, Mark Wills, Ferdia A Gallagher, Joanne L Jones
Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodeling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. In this article, we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods for determining T cell responses (i...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29286239/suppression-of-tumor-energy-supply-by-liposomal-nanoparticle-mediated-inhibition-of-aerobic-glycolysis
#14
Yinlong Zhang, JingYan Wei, Jiaqi Xu, Wei Sun Leong, Guangna Liu, Tianjiao Ji, Zhiqiang Cheng, Jing Wang, Jiayan Lang, Ying Zhao, Linhao You, Xiao Zhao, Taotao Wei, Greg J Anderson, Sheng Qi, Jing Kong, Guangjun Nie, Suping Li
Aerobic glycolysis enables cancer cells to rapidly take up nutrients (e.g., nucleotides, amino acids, lipids) and incorporate them into the biomass needed to produce a new cell. In contrast to existing chemotherapy/radiotherapy strategies, inhibiting aerobic glycolysis to limit ATP yield is a highly efficient approach for suppressing tumor cell proliferation. However, most, if not all, current inhibitors of aerobic glycolysis cause significant adverse effects, due to their nonspecific delivery and distribution to non-diseased organs, low bioavailability and a narrow therapeutic window...
December 29, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29275212/nrf2-facilitates-breast-cancer-cell-growth-via-hif1%C3%A9-mediated-metabolic-reprogramming
#15
Hong-Sheng Zhang, Guang-Yuan Du, Zhong-Guo Zhang, Zhen Zhou, Hong-Liang Sun, Xiao-Ying Yu, Yu-Ting Shi, Dan-Ning Xiong, Hu Li, Ying-Hui Huang
High aerobic glycolysis not only provides energy to breast cancer cells, but also supports their anabolic growth. The redox sensitive transcription factor NRF2 is over-expressed in multiple cancers, including breast cancer. It is unclear whether NRF2 could promote breast cancer cell growth through enhancing glycolysis. In this study, we found that NRF2 and HIF1α mRNA and protein levels were significantly increased in MCF-7 and MDA-MB-231 breast cancer cells as compared to MCF-10A benign breast epithelial cells...
December 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29259242/photoreceptor-metabolic-reprogramming-provides-survival-advantage-in-acute-stress-while-causing-chronic-degeneration
#16
Thomas J Wubben, Mercy Pawar, Andrew Smith, Kevin Toolan, Heather Hager, Cagri G Besirli
Photoreceptor death is the root cause of vision loss in many retinal disorders, and there is an unmet need for neuroprotective modalities to improve photoreceptor survival. The biosynthetic requirement of photoreceptors is among the highest in the body, and to meet this demand, photoreceptors maintain their ability to perform aerobic glycolysis. This highly regulated form of glycolysis allows cells to efficiently budget their metabolic needs and may be a critical link between photoreceptor function and survival...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29227990/correction-novel-role-of-nox-in-supporting-aerobic-glycolysis-in-cancer-cells-with-mitochondrial-dysfunction-and-as-a-potential-target-for-cancer-therapy
#17
Weiqin Lu, Yumin Hu, Gang Chen, Zhao Chen, Hui Zhang, Feng Wang, Li Feng, Helene Pelicano, Hua Wang, Michael J Keating, Jinsong Liu, Wallace McKeehan, Huamin Wang, Yongde Luo, Peng Huang
[This corrects the article DOI: 10.1371/journal.pbio.1001326.].
December 2017: PLoS Biology
https://www.readbyqxmd.com/read/29221849/molecular-regulation-of-fatty-acid-oxidation-in-skeletal-muscle-during-aerobic-exercise
#18
REVIEW
Anne-Marie Lundsgaard, Andreas Mæchel Fritzen, Bente Kiens
This review summarizes how fatty acid (FA) oxidation is regulated in skeletal muscle during exercise. From the available evidence it seems that acetyl-CoA availability in the mitochondrial matrix adjusts FA oxidation to exercise intensity and duration. This is executed at the step of mitochondrial fatty acyl import, as the extent of acetyl group sequestration by carnitine determines the availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1) reaction. The rate of glycolysis seems therefore to be central to the amount of β-oxidation-derived acetyl-CoA that is oxidized in the tricarboxylic acid (TCA) cycle...
January 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29221144/ucp2-overexpression-enhanced-glycolysis-via-activation-of-pfkfb2-during-skin-cell-transformation
#19
Annapoorna Sreedhar, Petra Petruska, Sumitra Miriyala, Manikandan Panchatcharam, Yunfeng Zhao
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane transporter which is often upregulated in human cancers. However, how this anion transporter affects tumorigenesis is not well understood. Using the skin cell transformation JB6 model, we demonstrated that UCP2 overexpression activated phosphofructokinase 2/fructose-2,6-bisphosphatase 2 (PFKFB2), a key regulator of glycolysis. In conjunction, upregulation of PFKFB2 expression correlated with elevated fructose 2,6-bisphosphate (Fru-2,6-P2) levels, 6-phosphofructo-1-kinase (PFK-1) activity, glucose uptake, and lactate production...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29219210/bioenergetic-regulation-of-microglia
#20
REVIEW
Soumitra Ghosh, Erika Castillo, Elma S Frias, Raymond A Swanson
Microglia have diverse actions, ranging from synapse pruning in development to cytotoxic effects in disease. Brain energy metabolism and substrate availability vary under normal and disease states, but how these variations influence microglial function is relatively unknown. Microglia, like most other cell types, express the full complement of gene products required for both glycolytic and oxidative metabolism. Evidence suggests that microglia increase aerobic glycolysis and decrease respiration when activated by various stimuli...
December 8, 2017: Glia
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