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Aerobic glycolysis

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https://www.readbyqxmd.com/read/28543190/effects-of-shrna-mediated-silencing-of-pkm2-gene-on-aerobic-glycolysis-cell-migration-cell-invasion-and-apoptosis-in-colorectal-cancer-cells
#1
Xiao-Ling Yan, Xue-Bin Zhang, Ran Ao, Lin Guan
This study aims to explore the effects of shRNA-mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT-PCR, Western blotting and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector and PKM2-shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose-6-phosphate dehydrogenase (G-6-PD) coupled colorimetric assay and enzyme coupling rate method...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28541512/the-interplay-between-metabolic-remodeling-and-immune-regulation-in-glioblastoma
#2
Pravin Kesarwani, Shiva Kant, Antony Prabhu, Prakash Chinnaiyan
The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute towards a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) pathways...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28539549/the-metabolic-regulation-in-immune-cells-and-pathogenesis-of-systemic-lupus-erythematosus-%C3%A2-toward-new-therapeutic-applications%C3%A2
#3
Yusuke Takeshima, Yukiko Iwasaki, Tomohisa Okamura, Keishi Fujio, Kazuhiko Yamamoto
  The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28538105/linezolid-induced-lactic-acidosis-the-thin-line-between-bacterial-and-mitochondrial-ribosomes
#4
Alessandro Santini, Dario Ronchi, Manuela Garbellini, Daniela Piga, Alessandro Protti
Introduction - Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered - The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion - Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes...
May 24, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28536031/lactate-induces-osteoblast-differentiation-by-stabilization-of-hif1%C3%AE
#5
Yu Wu, Miaomiao Wang, Haihua Feng, Ying Peng, Jieyun Sun, Xiuxia Qu, Chunping Li
Aerobic glycolysis is involved in osteoblast differentiation induced by Wnt signaling or PTH treatment. However, it is still unclear whether lactate, the end product of aerobic glycolysis, plays any role in osteoblast differentiation. Herein we report that in cultures of osteoblast-lineage cells, lactate promoted alkaline phosphatase-positive cell formation, increased the activity of alkaline phosphatase, and induced the expression of osteocalcin. This osteoblast differentiation-inducing effect of lactate can be inhibited by blocking its entry into cells with MCT1 siRNA or inhibitors, and by interfering with its metabolism by using specific siRNAs for LDHB and PDH...
May 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28530221/micu1-drives-glycolysis-and-chemoresistance-in-ovarian-cancer
#6
Prabir K Chakraborty, Soumyajit Banerjee Mustafi, Xunhao Xiong, Shailendra Kumar Dhar Dwivedi, Vasyl Nesin, Sounik Saha, Min Zhang, Danny Dhanasekaran, Muralidharan Jayaraman, Robert Mannel, Kathleen Moore, Scott McMeekin, Da Yang, Rosemary Zuna, Kai Ding, Leonidas Tsiokas, Resham Bhattacharya, Priyabrata Mukherjee
Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca(2+) uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28528772/early-interleukin-6-enhances-hepatic-ketogenesis-in-appswe-psen1de9-mice-via-3-hydroxy-3-methylglutary-coa-synthase-2-signaling-activation-by-p38-nuclear-factor-%C3%AE%C2%BAb-p65
#7
Le Shi, Daina Zhao, Chen Hou, Yunhua Peng, Jing Liu, Shuangxi Zhang, Jiankang Liu, Jiangang Long
Alzheimer's disease (AD) is considered a multifactorial disease that affects the central nervous system and periphery. A decline in brain glucose metabolism is an early feature of AD and is accompanied by a phenotypic shift from aerobic glycolysis to ketogenesis. The liver is responsible for the generation of the ketone body. However, the mechanism that underlies hepatic ketogenesis in AD remains unclear. Here, we investigated hepatic ketogenesis during the early stage of AD pathogenesis in amyloid precursor protein (APPSWE) and presenilin (PSEN1dE9) (APP/PS1) mice...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28527624/understanding-aerobic-anaerobic-metabolism-in-caldibacillus-debilis-through-a-comparison-with-model-organisms
#8
Scott Wushke, Victor Spicer, Xiang Li Zhang, Brian Fristensky, Oleg V Krokhin, David B Levin, Nazim Cicek, Richard Sparling
Caldibacillus debilis GB1 is a facultative anaerobe isolated from a thermophilic aero-tolerant cellulolytic enrichment culture. There is a lack of representative proteomes of facultative anaerobic thermophilic Bacillaceae, exploring aerobic/anaerobic expression. The C. debilis GB1 genome was sequenced and annotated, and the proteome characterized under aerobic and anaerobic conditions while grown on cellobiose. The draft sequence of C. debilis GB1 contains a 3,340,752 bp chromosome and a 5,386 bp plasmid distributed over 49 contigs...
April 13, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#9
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven Jm Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey MacDonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511909/discovery-and-structure-guided-fragment-linking-of-4-2-3-dichlorobenzoyl-1-methyl-pyrrole-2-carboxamide-as-a-pyruvate-kinase-m2-activator
#10
Yumi Matsui, Isao Yasumatsu, Takashi Asahi, Takahiro Kitamura, Kazuo Kanai, Osamu Ubukata, Hitoshi Hayasaka, Sachiko Takaishi, Hiroyuki Hanzawa, Shinichi Katakura
Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic intermediates as building blocks for biosynthetic processes, and thereby supporting cell proliferation. Activation of PKM2 should invert aerobic glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has gained attention as a promising cancer therapy target. To obtain novel PKM2 activators, we conducted a high-throughput screening (HTS)...
May 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28508297/adaptation-to-stochastic-temporal-variations-in-intratumoral-blood-flow-the-warburg-effect-as-a-bet-hedging-strategy
#11
Curtis A Gravenmier, Miriam Siddique, Robert A Gatenby
While most cancers promote ingrowth of host blood vessels, the resulting vascular network usually fails to develop a mature organization, resulting in abnormal vascular dynamics with stochastic variations that include slowing, cessation, and even reversal of flow. Thus, substantial spatial and temporal variations in oxygen concentration are commonly observed in most cancers. Cancer cells, like all living systems, are subject to Darwinian dynamics such that their survival and proliferation are dependent on developing optimal phenotypic adaptations to local environmental conditions...
May 15, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28507025/cutting-edge-defective-aerobic-glycolysis-defines-the-distinct-effector-function-in-antigen-activated-cd8-recent-thymic-emigrants
#12
Cody A Cunningham, Tessa Bergsbaken, Pamela J Fink
Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have completed thymic selection and egress to the lymphoid periphery. RTEs are functionally distinct from their more mature but still naive T cell counterparts, because they exhibit dampened proliferation and reduced cytokine production upon activation. In this article, we show that, compared with more mature but still naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis following activation. Impaired metabolism underlies the reduced IFN-γ production observed in activated RTEs...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28500387/thermal-adaptation-strategies-of-the-extremophile-bacterium-thermus-filiformis-based-on-multi-omics-analysis
#13
F Mandelli, M B Couger, D A A Paixão, C B Machado, C M Carnielli, J A Aricetti, I Polikarpov, R Prade, C Caldana, A F Paes Leme, A Z Mercadante, D M Riaño-Pachón, Fabio Marcio Squina
Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot spring in New Zealand. The experimental study of the mechanisms of thermal adaptation is important to unveil response strategies of the microorganism to stress. In this study, the main pathways involved on T. filiformis thermoadaptation, as well as, thermozymes with potential biotechnological applications were revealed based on omics approaches. The strategy adopted in this study disclosed that pathways related to the carbohydrate metabolism were affected in response to thermoadaptation...
May 12, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/28498814/methyl-jasmonate-leads-to-necrosis-and-apoptosis-in-hepatocellular-carcinoma-cells-via-inhibition-of-glycolysis-and-represses-tumor-growth-in-mice
#14
Jingjing Li, Kan Chen, Fan Wang, Weiqi Dai, Sainan Li, Jiao Feng, Liwei Wu, Tong Liu, Shizan Xu, Yujing Xia, Jie Lu, Yingqun Zhou, Ling Xu, Chuanyong Guo
Methyl jasmonate has recently been found to have anti-cancer activity. Methyl jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. The results were applied to the in vivo treatment of nude mice with a satisfactory effect...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498807/knockdown-of-pkm2-and-gls1-expression-can-significantly-reverse-oxaliplatin-resistance-in-colorectal-cancer-cells
#15
Wei-Qun Lu, Ying-Ying Hu, Xiao-Ping Lin, Wei Fan
Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28491867/metabolic-reprogramming-in-glioma
#16
REVIEW
Marie Strickland, Elizabeth A Stoll
Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28488732/involvement-of-the-warburg-effect-in-non-tumor-diseases-processes
#17
REVIEW
Zhe Chen, Meiqing Liu, Lanfang Li, Linxi Chen
Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension. Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure...
May 10, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28488573/reduced-production-and-uptake-of-lactate-are-essential-for-the-ability-of-wnt5a-signaling-to-inhibit-breast-cancer-cell-migration-and-invasion
#18
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...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484812/metabolic-engineering-of-gluconobacter-oxydans-621h-for-increased-biomass-yield
#19
Ines Kiefler, Stephanie Bringer, Michael Bott
The obligatory aerobic acetic acid bacterium Gluconobacter oxydans incompletely oxidizes carbon sources regio- and stereoselectively in the periplasm and therefore is used industrially for oxidative biotransformations, e. g., in vitamin C production. However, it has a very low biomass yield as the oxidized products largely remain in the medium and cannot be used for anabolism. Cytoplasmic carbon metabolism occurs via the pentose phosphate pathway and the Entner-Doudoroff pathway, whereas glycolysis and the tricarboxylic acid cycle are incomplete...
May 8, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28484259/the-physiological-and-molecular-response-of-aurelia-sp-1-under-hypoxia
#20
Guoshan Wang, Yu Zhen, Zhigang Yu, Yan Shi, Qing Zhao, Jianyan Wang, Tiezhu Mi
Few studies have been published on the mechanisms of hypoxia response and tolerance in jellyfish, especially with respect to the regulatory mechanism at the molecular level. In this study, Aurelia sp.1, which is frequently found in Chinese coastal waters, was cultivated in a hypoxic system to determine the molecular mechanisms underlying its hypoxic response by studying the physiological activity, gene expression and metabolite contents in the prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) oxygen-sensing system...
May 8, 2017: Scientific Reports
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