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Lactate AND MCT4

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https://www.readbyqxmd.com/read/28471448/mir-1-suppresses-tumor-cell-proliferation-in-colorectal-cancer-by-inhibition-of-smad3-mediated-tumor-glycolysis
#1
Wanfu Xu, Zijing Zhang, Kejian Zou, Yang Cheng, Min Yang, Huan Chen, Hongli Wang, Junhong Zhao, Peiyu Chen, Liying He, Xinwen Chen, Lanlan Geng, Sitang Gong
Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28440446/temporal-and-spatial-changes-of-monocarboxylate-transporter-4-expression-in-the-hippocampal-ca1-region-following-transient-forebrain-ischemia-in-the-mongolian-gerbil
#2
Dae Young Yoo, Joon Ha Park, Kwon Young Lee, Hyun Jung Kwon, Hyo Young Jung, Jong Whi Kim, Dae Won Kim, Jung Hoon Choi, Seung Myung Moon, Yeo Sung Yoon, Moo-Ho Won, In Koo Hwang
Transient forebrain ischemia depletes glucose and oxygen levels in the brain. In this pathological condition, lactate serves an important role in cellular metabolism as the end product of glycolysis. The present study investigated the expression of monocarboxylate transporter 4 (MCT4) in lactate metabolism in the hippocampal CA1 region following induction of transient forebrain ischemia. MCT4 immunoreactivity was detected in CA1 pyramidal cells of the sham-operated group. Animals from the ischemic group exhibited a transient decrease in MCT4 immunoreactivity in the CA1 region between 30 min and 3 h following ischemia compared with the sham‑operated group...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28428273/assessing-prostate-cancer-aggressiveness-with-hyperpolarized-dual-agent-3d-dynamic-imaging-of-metabolism-and-perfusion
#3
Hsin-Yu Chen, Peder E Z Larson, Robert A Bok, Cornelius von Morze, Renuka Sriram, Romelyn Delos Santos, Justin Delos Santos, Jeremy W Gordon, Naeim Bahrami, Marcus Ferrone, John Kurhanewicz, Daniel B Vigneron
New magnetic resonance (MR) molecular imaging techniques offer the potential for non-invasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a 3D dynamic dual-agent hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) approach with (13)C-pyruvate and (13)C-urea to investigate differences in perfusion and metabolism between low and high grade tumors in the TRAMP transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28356703/differential-responses-of-choroidal-melanocytes-and-uveal-melanoma-cells-to-low-oxygen-conditions
#4
Cindy Weidmann, Jade Pomerleau, Laurence Trudel-Vandal, Solange Landreville
PURPOSE: Tissue culture is traditionally performed at atmospheric oxygen concentration (21%), which induces hyperoxic stress, as endogenous physiologic oxygen tension found in tissues varies between 2% and 9%. This discrepancy may lead to misinterpretation of results and may explain why effects observed in vitro cannot always be reproduced in vivo and vice versa. Only a few studies have been conducted in low physiologic oxygen conditions to understand the development and differentiation of cells from the eye...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28222424/1%C3%AE-25-oh-2d3-sensitive-cytosolic-ph-regulation-and-glycolytic-flux-in-human-endometrial-ishikawa-cells
#5
Ni Zeng, Yuetao Zhou, Shaqiu Zhang, Yogesh Singh, Bing Shi, Madhuri S Salker, Florian Lang
BACKGROUND/AIMS: Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions and lactate, which is in part accomplished by Na+/H+ exchangers, such as NHE1 and monocarboxylate transporters, such as MCT4...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28206968/intratumoral-lactate-metabolism-in-barrett-s-esophagus-and-adenocarcinoma
#6
Heikki Huhta, Olli Helminen, Sami Palomäki, Joonas H Kauppila, Juha Saarnio, Petri P Lehenkari, Tuomo J Karttunen
BACKGROUND: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. RESULTS: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185288/metformin-effects-on-head-and-neck-squamous-carcinoma-microenvironment-window-of-opportunity-trial
#7
Joseph Curry, Jennifer Johnson, Patrick Tassone, Marina Domingo Vidal, Diana Whitaker Menezes, John Sprandio, Mehri Mollaee, Paolo Cotzia, Ruth Birbe, Zhao Lin, Kurren Gill, Elizabeth Duddy, Tingting Zhan, Benjamin Leiby, Michelle Reyzer, David Cognetti, Adam Luginbuhl, Madalina Tuluc, Ubaldo Martinez-Outschoorn
OBJECTIVE: The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. STUDY DESIGN: Window of opportunity trial of metformin between diagnostic biopsy and resection...
February 10, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28148492/rest-interval-duration-does-not-influence-adaptations-in-acid-base-transport-proteins-following-10-weeks-of-sprint-interval-training-in-active-women
#8
Cian McGinley, David John Bishop
The removal of protons (H(+)) produced during intense exercise is important for skeletal muscle function, yet it remains unclear how best to structure exercise training to improve muscle pH regulation. We investigated whether 4 weeks of work-matched, sprint-interval training (SIT), performed 3 days per week, with either 1 min (Rest-1; n = 7) or 5 min (Rest-5; n = 7) of rest between sprints, influenced adaptations in acid/base transport protein content, non-bicarbonate muscle buffer capacity (βmin vitro), and exercise capacity in active women...
February 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28122719/high-intensity-intermittent-exercise-training-with-chlorella-intake-accelerates-exercise-performance-and-muscle-glycolytic-and-oxidative-capacity-in-rats
#9
Naoki Horii, Natsuki Hasegawa, Shumpei Fujie, Masataka Uchida, Eri Miyamoto-Mikami, Takeshi Hashimoto, Izumi Tabata, Motoyuki Iemitsu
The purpose of this study was to investigate the effect of chronic chlorella intake alone or in combination with high-intensity intermittent exercise (HIIE) training on exercise performance and muscle glycolytic and oxidative metabolism in rats. Forty male Sprague-Dawley rats were randomly assigned to the four groups: sedentary control, chlorella intake (0.5% chlorella powder in normal feed), HIIE training, and combination of HIIE training and chlorella intake for 6 wk (n = 10 each group). HIIE training comprised 14 repeats of a 20-s swimming session with a 10-s pause between sessions, while bearing a weight equivalent to 16% of body weight, 4 days/week...
April 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28107190/radiosynthesis-and-validation-of-%C3%A2-18f-3-fluoro-2-hydroxypropionate-18f-flac-as-a-pet-tracer-of-lactate-to-monitor-mct1-dependent-lactate-uptake-in-tumors
#10
Vincent F Van Hée, Daniel Labar, Gwenaël Dehon, Debora Grasso, Vincent Grégoire, Giulio G Muccioli, Raphaël Frédérick, Pierre Sonveaux
Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099149/clinically-relevant-hif-1%C3%AE-dependent-metabolic-reprogramming-in-oropharyngeal-squamous-cell-carcinomas-includes-coordinated-activation-of-caix-and-the-mir-210-iscu-signaling-axis-but-not-mct1-and-mct4-upregulation
#11
Inés Sáenz-de-Santa-María, Cristóbal Bernardo-Castiñeira, Pablo Secades, Sandra Bernaldo-de-Quirós, Juan Pablo Rodrigo, Aurora Astudillo, María-Dolores Chiara
Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#12
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28046118/transcriptome-analysis-identifies-key-metabolic-changes-in-the-hooded-seal-cystophora-cristata-brain-in-response-to-hypoxia-and-reoxygenation
#13
Mariana Leivas Müller Hoff, Andrej Fabrizius, Nicole U Czech-Damal, Lars P Folkow, Thorsten Burmester
The brain of diving mammals tolerates low oxygen conditions better than the brain of most terrestrial mammals. Previously, it has been demonstrated that the neurons in brain slices of the hooded seal (Cystophora cristata) withstand hypoxia longer than those of mouse, and also tolerate reduced glucose supply and high lactate concentrations. This tolerance appears to be accompanied by a shift in the oxidative energy metabolism to the astrocytes in the seal while in terrestrial mammals the aerobic energy production mainly takes place in neurons...
2017: PloS One
https://www.readbyqxmd.com/read/27993896/reexamining-cancer-metabolism-lactate-production-for-carcinogenesis-could-be-the-purpose-and-explanation-of-the-warburg-effect
#14
Iñigo San-Millán, George A Brooks
Herein, we use lessons learned in exercise physiology and metabolism to propose that augmented lactate production ('lactagenesis'), initiated by gene mutations, is the reason and purpose of the Warburg Effect and that dysregulated lactate metabolism and signaling are the key elements in carcinogenesis. Lactate-producing ('lactagenic') cancer cells are characterized by increased aerobic glycolysis and excessive lactate formation, a phenomenon described by Otto Warburg 93 years ago, which still remains unexplained...
February 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/27860283/integration-of-a-proton-antenna-facilitates-transport-activity-of-the-monocarboxylate-transporter-mct4
#15
Sina Ibne Noor, Jacques Pouyssegur, Joachim W Deitmer, Holger M Becker
Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of high-energy metabolites like lactate and pyruvate and are expressed in nearly every mammalian tissue. We have shown previously that transport activity of MCT4 is enhanced by carbonic anhydrase II (CAII), which has been suggested to function as a 'proton antenna' for the transporter. In the present study, we tested whether creation of an endogenous proton antenna by introduction of a cluster of histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate MCT4 transport activity when heterologously expressed in Xenopus oocytes...
November 15, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27859555/pyruvate-cellular-uptake-and-enzymatic-conversion-probed-by-dissolution-dnp-nmr-the-impact-of-overexpressed-membrane-transporters
#16
Riccardo Balzan, Laetitia Fernandes, Laetitia Pidial, Arnaud Comment, Bertrand Tavitian, Paul R Vasos
Pyruvate membrane crossing and its lactate dehydrogenase-mediated conversion to lactate in cells featuring different levels of expression of membrane monocarboxylate transporters (MCT4) were probed by dissolution dynamic nuclear polarization-enhanced NMR. Hyperpolarized (13) C-1-labeled pyruvate was transferred to suspensions of rodent tumor cell carcinoma, cell line 39. The pyruvate-to-lactate conversion rate monitored by dissolution dynamic nuclear polarization-NMR in carcinoma cells featuring native MCT4 expression level was lower than the rate observed for cells in which the human MCT4 gene was overexpressed...
November 12, 2016: Magnetic Resonance in Chemistry: MRC
https://www.readbyqxmd.com/read/27843454/localisation-of-lactate-transporters-in-rat-and-rabbit-placentae
#17
Nigel P Moore, Catherine A Picut, Jeffrey H Charlap
The distribution of monocarboxylate transporter (MCT) isoforms 1 and 4, which mediate the plasmalemmal transport of l-lactic and pyruvic acids, has been identified in the placentae of rats and rabbits at different ages of gestation. Groups of three pregnant Sprague-Dawley rats and New Zealand White rabbits were sacrificed on gestation days (GD) 11, 14, 18, or 20 and on GD 13, 18, or 28, respectively. Placentae were removed and processed for immunohistochemical detection of MCT1 and MCT4. In the rat, staining for MCT1 was associated with lakes and blood vessels containing enucleated red blood cells (maternal vessels) while staining for MCT4 was associated with vessels containing nucleated red blood cells (embryofoetal vessels)...
2016: International Journal of Cell Biology
https://www.readbyqxmd.com/read/27742804/influence-of-training-intensity-on-adaptations-in-acid-base-transport-proteins-muscle-buffer-capacity-and-repeated-sprint-ability-in-active-men
#18
Cian McGinley, David J Bishop
McGinley C, Bishop DJ. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men. J Appl Physiol 121: 1290-1305, 2016. First published October 14, 2016; doi:10.1152/japplphysiol.00630.2016-This study measured the adaptive response to exercise training for each of the acid-base transport protein families, including providing isoform-specific evidence for the monocarboxylate transporter (MCT)1/4 chaperone protein basigin and for the electrogenic sodium-bicarbonate cotransporter (NBCe)1...
December 1, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27660270/hyperpalatable-diet-and-physical-exercise-modulate-the-expression-of-the-glial-monocarboxylate-transporters-mct1-and-4
#19
Luis V Portela, Andressa W Brochier, Clarissa B Haas, Afonso Kopczynski de Carvalho, Jussania A Gnoato, Eduardo R Zimmer, Eduardo Kalinine, Luc Pellerin, Alexandre P Muller
Hyperpalatable diets (HP) impair brain metabolism, and regular physical exercise has an apparent opposite effect. Here, we combined a prior long-term exposure to HP diet followed by physical exercise and evaluated the impact on some neuroenergetic components and on cognitive performance. We assessed the extracellular lactate concentration, expression of monocarboxylate transporters (MCTs), pyruvate dehydrogenase (PDH), and mitochondrial function in the hippocampus. Male C57BL/6J mice were fed 4 months with HP or a control diet...
September 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27623078/unique-metabolic-features-of-pancreatic-cancer-stroma-relevance-to-the-tumor-compartment-prognosis-and-invasive-potential
#20
Erik S Knudsen, Uthra Balaji, Elizaveta Freinkman, Peter McCue, Agnieszka K Witkiewicz
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment...
November 29, 2016: Oncotarget
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