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Lactate AND HIF-1

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https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#1
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/28762551/monocarboxylate-transporter-1-is-a-key-player-in-glioma-endothelial-cell-crosstalk
#2
Vera Miranda-Gonçalves, Filipa Bezerra, Raquel Costa-Almeida, Marta Freitas-Cunha, Raquel Soares, Olga Martinho, Rui M Reis, Céline Pinheiro, Fátima Baltazar
Glioblastoma (GBM) is one of the most glycolytic and angiogenic human tumours, characteristics that contribute to the poor prognosis associated with this type of tumour. A lactate shuttle has been described between tumour cells and endothelial cells (ECs), with the monocarboxylate transporters (MCTs) acting as important players in this tumour-EC communication. In this study, we aimed to understand how the tumour microenvironment modulates EC metabolism, and to characterize the role of MCTs in the glioma-brain EC crosstalk...
August 1, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28753560/enhancement-of-the-anti-tumor-activity-of-fgfr1-inhibition-in-squamous-cell-lung-cancer-by-targeting-downstream-signaling-involved-in-glucose-metabolism
#3
Claudia Fumarola, Daniele Cretella, Silvia La Monica, Mara A Bonelli, Roberta Alfieri, Cristina Caffarra, Federico Quaini, Denise Madeddu, Angela Falco, Andrea Cavazzoni, Graziana Digiacomo, Giulia Mazzaschi, Valentina Vivo, Elisabetta Barocelli, Marcello Tiseo, Pier Giorgio Petronini, Andrea Ardizzoni
Fibroblast Growth Factor Receptor (FGFR) signaling is a complex pathway which controls several processes, including cell proliferation, survival, migration, and metabolism. FGFR1 signaling is frequently deregulated via amplification/over-expression in NSCLC of squamous histotype (SQCLC), however its inhibition has not been successfully translated in clinical setting. We determined whether targeting downstream signaling implicated in FGFR1 effects on glucose metabolism potentiates the anti-tumor activity of FGFR1 inhibition in SQCLC...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28741686/gpr55-receptor-antagonist-decreases-glycolytic-activity-in-panc-1-pancreatic-cancer-cell-line-and-tumor-xenografts
#4
Michel Bernier, Jonathan Catazaro, Nagendra S Singh, Artur Wnorowski, Anna Boguszewska-Czubara, Krzysztof Jozwiak, Robert Powers, Irving W Wainer
The Warburg effect is a predominant metabolic pathway in cancer cells characterized by enhanced glucose uptake and its conversion to l-lactate and is associated with upregulated expression of HIF-1α and activation of the EGFR-MEK-ERK, Wnt-β-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1-naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55 receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and tumors...
July 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28737429/hif-1%C3%AE-inhibition-by-diethylstilbestrol-and-its-polyacetal-conjugate-in-hypoxic-prostate-tumour-cells-insights-from-nmr-metabolomics
#5
Ana Armiñán, Luís Mendes, Joana Carrola, Julie Movellan, María J Vicent, Iola F Duarte
In this study, we have employed (1)H NMR metabolomics to assess the metabolic responses of PC3 prostate tumour cells to hypoxia and to pharmacological HIF-1α inhibition by DES or its polyacetal conjugate tert-DES. Oxygen deprivation prompted a number of changes in intracellular composition and metabolic activity, mainly reflecting upregulated glycolysis, amino acid catabolism and other compensatory mechanisms used by hypoxic cells to deal with oxidative imbalance and energy deficit. Cell treatment with a non-cytotoxic concentration of DES, under hypoxia, triggered significant changes in 17 metabolites...
July 24, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28721162/the-influence-of-rapamycin-on-the-early-cardioprotective-effect-of-hypoxic-preconditioning-on-cardiomyocytes
#6
Jiang Wang, YiLiyaer Maimaitili, Hong Zheng, Jin Yu, Hai Guo, Hai-Ping Ma, Chun-Ling Chen
INTRODUCTION: The purpose of this study was to examine the effects of rapamycin on the cardioprotective effect of hypoxic preconditioning (HPC) and on the mammalian target of rapamycin (mTOR)-mediated hypoxia-inducible factor 1 (HIF-1) signaling pathway. MATERIAL AND METHODS: Primary cardiomyocytes were isolated from rat pups and underwent rapamycin and/or HPC, followed by hypoxia/re-oxygenation (H/R) injury. Cell viability and cell injury were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and qRT-PCR was used to measure HIF-1α and mTOR mRNA expression...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28689265/aerobic-glycolysis-hypothesis-through-wnt-beta-catenin-pathway-in-exudative-age-related-macular-degeneration
#7
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Exudative age-related macular degeneration (AMD) is characterized by molecular mechanisms responsible for the initiation of choroidal neovascularization (CNV). Inflammatory processes are associated with upregulation of the canonical WNT/beta-catenin pathway in exudative AMD. We focus this review on the link between WNT/beta-catenin pathway activation and neovascular progression in exudative AMD through activation of aerobic glycolysis for production of angiogenic factors. Increased WNT/beta-catenin pathway involves hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2)...
August 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28679957/socs1-is-a-negative-regulator-of-metabolic-reprogramming-during-sepsis
#8
Annie Rocio Piñeros Alvarez, Nicole Glosson-Byers, Stephanie Brandt, Soujuan Wang, Hector Wong, Sarah Sturgeon, Brian Paul McCarthy, Paul R Territo, Jose Carlos Alves-Filho, C Henrique Serezani
Sepsis can induce an overwhelming systemic inflammatory response, resulting in organ damage and death. Suppressor of cytokine signaling 1 (SOCS1) negatively regulates signaling by cytokine receptors and Toll-like receptors (TLRs). However, the cellular targets and molecular mechanisms for SOCS1 activity during polymicrobial sepsis are unknown. To address this, we utilized a cecal ligation and puncture (CLP) model for sepsis; C57BL/6 mice subjected to CLP were then treated with a peptide (iKIR) that binds the SOCS1 kinase inhibitory region (KIR) and blocks its activity...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28651317/effects-of-multi-environmental-factors-on-physiological-and-biochemical-responses-of-large-yellow-croaker-larimichthys-crocea
#9
Qian-Feng Wang, Wei-Liang Shen, Cheng Liu, Dan-Li Mu, Xiong-Fei Wu, Nian-Gang Guo, Jun-Quan Zhu
Land-based recirculating aquaculture systems (RAS) and cage culture are important methods of Larimichthys crocea production. The effects of environmental factors on physiological and biochemical aspects of L. crocea require clarification. Temperature and salinity are controlled in RAS and directly affect L. crocea growth and survival. To explore optimal parameters, the oxygen consumption rate (RO), ammonium excretion rate (RN), and O/N ratio at different temperatures (8, 14, 20, 26, and 32 °C) and salinities (5, 15, 25, and 35‰) were determined...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28642716/effects-of-acute-hypoxia-and-reoxygenation-on-physiological-and-immune-responses-and-redox-balance-of-wuchang-bream-megalobrama-amblycephala-yih-1955
#10
Nan Chen, Meng Wu, Guo-Pan Tang, Hui-Juan Wang, Chun-Xiao Huang, Xin-Jie Wu, Yan He, Bao Zhang, Cui-Hong Huang, Hong Liu, Wei-Min Wang, Huan-Ling Wang
To study Megalobrama amblycephala adaption to water hypoxia, the changes in physiological levels, innate immune responses, redox balance of M.amblycephala during hypoxia were investigated in the present study. When M. amblycephala were exposed to different dissolved oxygen (DO) including control (DO: 5.5 mg/L) and acute hypoxia (DO: 3.5 and 1.0 mg/L, respectively), hemoglobin (Hb), methemoglobin (MetHb), glucose, Na(+), succinatedehydrogenase (SDH), lactate, interferon alpha (IFNα), and lysozyme (LYZ), except hepatic glycogen and albumin gradually increased with the decrease of DO level...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28642579/regulation-of-glycolysis-in-brown-adipocytes-by-hif-1%C3%AE
#11
Astrid L Basse, Marie S Isidor, Sally Winther, Nina B Skjoldborg, Maria Murholm, Elise S Andersen, Steen B Pedersen, Christian Wolfrum, Bjørn Quistorff, Jacob B Hansen
Brown adipose tissue takes up large amounts of glucose during cold exposure in mice and humans. Here we report an induction of glucose transporter 1 expression and increased expression of several glycolytic enzymes in brown adipose tissue from cold-exposed mice. Accordingly, these genes were also induced after β-adrenergic activation of cultured brown adipocytes, concomitant with accumulation of hypoxia inducible factor-1α (HIF-1α) protein levels. HIF-1α accumulation was dependent on uncoupling protein 1 and generation of mitochondrial reactive oxygen species...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610954/feedback-regulation-of-aldoa-activates-the-hif-1%C3%AE-mmp9-axis-to-promote-lung-cancer-progression
#12
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yi Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28598398/right-vs-left-sided-metastatic-colorectal-cancer-differences-in-tumor-biology-and-bevacizumab-efficacy
#13
Paola Ulivi, Emanuela Scarpi, Elisa Chiadini, Giorgia Marisi, Martina Valgiusti, Laura Capelli, Andrea Casadei Gardini, Manlio Monti, Silvia Ruscelli, Giovanni Luca Frassineti, Daniele Calistri, Dino Amadori, Alessandro Passardi
There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B)...
June 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28590414/mtdna-as-a-mediator-for-expression-of-hypoxia-inducible-factor-1%C3%AE-and-ros-in-hypoxic-neuroblastoma-cells
#14
Chung-Wen Kuo, Meng-Han Tsai, Tsu-Kung Lin, Mao-Meng Tiao, Pei-Wen Wang, Jiin-Haur Chuang, Shang-Der Chen, Chia-Wei Liou
Mitochondria consume O₂ to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28569777/the-novel-hypoxia-inducible-factor-1%C3%AE-inhibitor-idf-11774-regulates-cancer-metabolism-thereby-suppressing-tumor-growth
#15
Hyun Seung Ban, Bo-Kyung Kim, Hongsub Lee, Hwan Mook Kim, Dipesh Harmalkar, Miso Nam, Song-Kyu Park, Kiho Lee, Joon-Tae Park, Inhyub Kim, Kyeong Lee, Geum-Sook Hwang, Misun Won
HIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. We previously developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, a clinical candidate for cancer therapy. We also reported that IDF-1174 inhibited HSP70 chaperone activity and suppressed accumulation of HIF-1α. In this study, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28495754/phd3-is-a-transcriptional-coactivator-of-hif-1%C3%AE-in-nucleus-pulposus-cells-independent-of-the-pkm2-jmjd5-axis
#16
Zachary R Schoepflin, Elizabeth S Silagi, Irving M Shapiro, Makarand V Risbud
The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1α cofactor is controversial and remains unknown in skeletal tissues. We investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain--containing protein (JMJD5) axis. PHD3(-/-) mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28485159/fbp1-modulates-cell-metabolism-of-breast-cancer-cells-by-inhibiting-the-expression-of-hif-1%C3%AE
#17
L Shi, C He, Z Li, Z Wang, Q Zhang
This study aimed to investigate the function of fructose-1, 6-bisphosphatase 1 (FBP1) in regulating cell growth and metabolism through hypoxia-inducible factor 1α (HIF-1α)-dependent hypoxic response in breast cancer cells. Two human breast carcinoma cell lines, including luminal-like cell line MCF-7 and basal-like cell line MDA-MB-468, were cultured under hypoxia condition, then the expressions of FBP1 and HIF-1α were detected by western blotting. In addition, up-regulated FPB1 in MDA-MB-468 cells were induced by lentivirus...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28484259/the-physiological-and-molecular-response-of-aurelia-sp-1-under-hypoxia
#18
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
https://www.readbyqxmd.com/read/28471448/mir-1-suppresses-tumor-cell-proliferation-in-colorectal-cancer-by-inhibition-of-smad3-mediated-tumor-glycolysis
#19
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/28463588/the-lactate-dehydrogenase-inhibitor-gossypol-inhibits-radiation-induced-pulmonary-fibrosis
#20
Jennifer L Judge, Shannon H Lacy, Wei-Yao Ku, Kristina M Owens, Eric Hernady, Thomas H Thatcher, Jacqueline P Williams, Richard P Phipps, Patricia J Sime, R Matthew Kottmann
Exposure of the lung to ionizing radiation that occurs in radiotherapy, as well as after accidental or intentional mass casualty incident can result in pulmonary fibrosis, which has few treatment options. Pulmonary fibrosis is characterized by an accumulation of extracellular matrix proteins that create scar tissue. Although the mechanisms leading to radiation-induced pulmonary fibrosis remain poorly understood, one frequent observation is the activation of the profibrotic cytokine transforming growth factor-beta (TGF-β)...
July 2017: Radiation Research
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