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Lactate AND HIF-1

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https://www.readbyqxmd.com/read/28193910/hif1-2%C3%AE-mediates-hypoxia-induced-ldha-expression-in-human-pancreatic-cancer-cells
#1
Xin-Gang Cui, Zhi-Tao Han, Shao-Hui He, Xing-da Wu, Tian-Rui Chen, Cheng-Hao Shao, Dan-Lei Chen, Ning Su, Yuan-Ming Chen, Ting Wang, Jing Wang, Dian-Wen Song, Wang-Jun Yan, Xing-Hai Yang, Tie-Long Liu, Hai-Feng Wei, Jianru Xiao
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages...
10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173667/-expression-of-hypoxia-inducible-factor-1%C3%AE-glucose-transporter-1-and-lactate-dehydrogenase-5-in-colorectal-cancer-and-clinicopathologic-significance
#2
T Y Yang, L S Hao, D Z Guo
Objective: To investigate the expression and clinicopathological significance of hypoxia-inducible factor 1 alpha (HIF-1α), glucose transporter 1(GLUT-1) and lactate dehydrogenase(LDH)-5 in colorectal cancer. Methods: The expression levels of HIF-1α, GLUT-1 and LDH-5 were detected by immunohistochemical staining in 142 specimens of human carcinoma in comparison with adjacent normal tissues. Results: The expression levels of HIF-1α(78.2%, 111/142), GLUT-1(75.4%, 107/142) and LDH-5(68.3%, 97/142) were higher in tumor tissues than in adjacent normal tissues(14...
February 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28170315/cytoplasmic-irradiation-induces-metabolic-shift-in-human-small-airway-epithelial-cells-via-activation-of-pim-1-kinase
#3
Jinhua Wu, Qin Zhang, Yen-Ruh Wuu, Sirui Zou, Tom K Hei
The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells...
February 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/27926487/egf-induces-epithelial-mesenchymal-transition-and-cancer-stem-like-cell-properties-in-human-oral-cancer-cells-via-promoting-warburg-effect
#4
Qilin Xu, Qunzhou Zhang, Yasutaka Ishida, Souren Hajjar, Xudong Tang, Haoran Shi, Chi V Dang, Anh D Le
"Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27803454/isorhamnetin-inhibits-reactive-oxygen-species-dependent-hypoxia-inducible-factor-hif-1%C3%AE-accumulation
#5
Suho Seo, Kyuhwa Seo, Sung Hwan Ki, Sang Mi Shin
Isorhamnetin is a flavonoid metabolite of quercetin and isolated from water dropwort (Oenanthe javanica, Umbelliferae). It has been reported that isorhamnetin exerts beneficial effects including antioxidant, anti-inflammatory, and anti-proliferative activities. The present study investigated whether the antioxidant activity of isorhamnetin is correlated with its anti-cancer effects on colorectal cancer cells. Isorhamnetin significantly repressed cobalt chloride (CoCl2)- or hypoxia-induced hypoxia inducible factor-1α (HIF-1α) accumulation in HCT116 and HT29 cells...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27800513/preconditioning-with-ethyl-3-4-dihydroxybenzoate-augments-aerobic-respiration-in-rat-skeletal-muscle
#6
Charu Nimker, Deependra Pratap Singh, Deepika Saraswat, Anju Bansal
Muscle respiratory capacity decides the amount of exertion one's skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model...
2016: Hypoxia
https://www.readbyqxmd.com/read/27748854/hypoxia-induces-glucose-uptake-and-metabolism-of-adipose%C3%A2-derived-stem-cells
#7
Hyoung Sook Park, Ji Hye Kim, Bo Kyung Sun, Sun U Song, Wonhee Suh, Jong-Hyuk Sung
It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose‑derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27602585/human-cytomegalovirus-encoded-chemokine-receptor-us28-activates-the-hif-1%C3%AE-pkm2-axis-in-glioblastoma-cells
#8
Raymond H de Wit, Azra Mujić-Delić, Jeffrey R van Senten, Alberto Fraile-Ramos, Marco Siderius, Martine J Smit
The human cytomegalovirus (HCMV) encoded chemokine receptor US28 promotes tumorigenesis through activation of various proliferative and angiogenic signaling pathways. Upon infection, US28 displays constitutive activity and signals in a G protein-dependent manner, hijacking the host's cellular machinery. In tumor cells, the hypoxia inducible factor-1α/pyruvate kinase M2 (HIF-1α/PKM2) axis plays an important role by supporting proliferation, angiogenesis and reprogramming of energy metabolism. In this study we show that US28 signaling results in activation of the HIF-1α/PKM2 feedforward loop in fibroblasts and glioblastoma cells...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27601172/pathways-involved-in-oxygen-glucose-deprivation-damage-of-astrocytes
#9
Shuyong Wei, Jie Tong, Qiang Xue, Yang Liu, Xiaoyu Xu
This present paper focus on transcriptome changes of astrocytes before and after oxygen glucose deprivation (OGD) injury. Cortical astrocytes of Sprague-Dawley (SD) rats were cultured in OGD condition for 6 h, and the damage of cells was analyzed by cell's activity detection, lactate dehydrogenase leakage rate detection, annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) apoptosis detection, and transcriptome change detection through Affymetrix GeneChip Rat Genome 230 2.0 Array; some regulated genes were detected by quantitative real-time polymerase chain reaction (qPCR)...
January 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27559047/lactic-acid-suppresses-il-33-mediated-mast-cell-inflammatory-responses-via-hypoxia-inducible-factor-1%C3%AE-dependent-mir-155-suppression
#10
Daniel Abebayehu, Andrew J Spence, Amina Abdul Qayum, Marcela T Taruselli, Jamie J A McLeod, Heather L Caslin, Alena P Chumanevich, Elizabeth Motunrayo Kolawole, Anuya Paranjape, Bianca Baker, Victor S Ndaw, Brian O Barnstein, Carole A Oskeritzian, Scott A Sell, John J Ryan
Lactic acid (LA) is present in tumors, asthma, and wound healing, environments with elevated IL-33 and mast cell infiltration. Although IL-33 is a potent mast cell activator, how LA affects IL-33-mediated mast cell function is unknown. To investigate this, mouse bone marrow-derived mast cells were cultured with or without LA and activated with IL-33. LA reduced IL-33-mediated cytokine and chemokine production. Using inhibitors for monocarboxylate transporters (MCT) or replacing LA with sodium lactate revealed that LA effects are MCT-1- and pH-dependent...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27521225/lactate-induced-hif-1%C3%AE-prmt1-cross-talk-affects-mhc-i-expression-in-monocytes
#11
Piyushi Gupta, Ankita Singh, Pruthvi Gowda, Sadashib Ghosh, Arpita Chatterjee, Ellora Sen
Tumor infiltrating monocytes play a crucial role in tumor immune surveillance. As lactate is an important component of the tumor milieu, we investigated its role in the transcriptional regulation of MHC I which is crucial for mounting effective immune responses against tumors. Lactate elevated MHC class I expression in monocytes. Increase in HLAB expression was concomitant with increase in HIF-1α and decrease in PRMT1 levels. Interestingly, a reciprocal relationship was observed between PRMT1 and HIF-1α. While HIF-1α inhibition decreased lactate induced MHC I, both pharmacological inhibition and siRNA mediated knockdown of PRMT1 upregulated HLAB levels...
October 1, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27510037/acidic-ph-is-a-metabolic-switch-for-2-hydroxyglutarate-generation-and-signaling
#12
Sergiy M Nadtochiy, Xenia Schafer, Dragony Fu, Keith Nehrke, Joshua Munger, Paul S Brookes
2-Hydroxyglutarate (2-HG) is an important epigenetic regulator, with potential roles in cancer and stem cell biology. The d-(R)-enantiomer (d-2-HG) is an oncometabolite generated from α-ketoglutarate (α-KG) by mutant isocitrate dehydrogenase, whereas l-(S)-2-HG is generated by lactate dehydrogenase and malate dehydrogenase in response to hypoxia. Because acidic pH is a common feature of hypoxia, as well as tumor and stem cell microenvironments, we hypothesized that pH may regulate cellular 2-HG levels. Herein we report that cytosolic acidification under normoxia moderately elevated 2-HG in cells, and boosting endogenous substrate α-KG levels further stimulated this elevation...
September 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27447861/potential-role-of-the-n-myc-downstream-regulated-gene-family-in-reprogramming-cancer-metabolism-under-hypoxia
#13
REVIEW
Ga Young Lee, Yang-Sook Chun, Hyun-Woo Shin, Jong-Wan Park
Metabolic reprogramming toward aerobic glycolysis and lactate fermentation supplies cancer cells with intermediate metabolites, which are used as macromolecule precursors. The oncogene MYC contributes to such aerobic metabolism by activating the expression of numerous genes essential for glycolysis and mitochondrial biogenesis. However, to survive and evolve in a hypoxic tumor milieu, cancer cells must revise MYC-driven metabolism because the mitochondrial respiratory chain provides free electrons to generate oxygen free radicals with inefficient production of ATP due to oxygen depletion...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27434126/current-relevance-of-hypoxia-in-head-and-neck-cancer
#14
REVIEW
Marius G Bredell, Jutta Ernst, Ilhem El-Kochairi, Yuliya Dahlem, Kristian Ikenberg, Desiree M Schumann
Head and Neck cancer (HNC) is a complex mix of cancers and one of the more common cancers with a relatively poor prognosis. One of the factors that may assist us in predicting survival and allow us to adjust our treatment strategies is the presence of tumor hypoxia. In this overview we aim to evaluate the current evidence and potential clinical relevance of tumor hypoxia in head and neck cancer according to an extensive search of current literature.An abundance of evidence and often contradictory evidence is found in the literature...
August 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27422990/the-von-hippel-lindau-chuvash-mutation-in-mice-alters-cardiac-substrate-and-high-energy-phosphate-metabolism
#15
Mary Slingo, Mark Cole, Carolyn Carr, Mary K Curtis, Michael Dodd, Lucia Giles, Lisa C Heather, Damian Tyler, Kieran Clarke, Peter A Robbins
Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF pathway manipulation is of therapeutic interest; however, global systemic upregulation of HIF may have as yet unknown effects on multiple processes. We used a mouse model of Chuvash polycythemia (CP), a rare genetic disorder that modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An integrated in and ex vivo approach was employed...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27385728/id2-mediates-the-transforming-growth-factor-%C3%AE-1-induced-warburg-like-effect-seen-in-the-peritoneum-of-women-with-endometriosis
#16
Vicky J Young, Syed F Ahmad, Jeremy K Brown, W Colin Duncan, Andrew W Horne
STUDY QUESTION: Is inhibitor of DNA-binding protein 2 (ID2) a mediator of the transforming growth factor (TGF)-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis? SUMMARY ANSWER: The TGF-β1-induced changes in the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis are mediated through the ID2 pathway. WHAT IS KNOWN ALREADY: TGF-β1 induces the metabolic conversion of glucose to lactate via aerobic glycolysis (the 'Warburg effect') in the peritoneum of women with endometriosis, through increased expression of the transcription factor hypoxia inducible factor α (HIF-1α)...
September 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/27342248/the-promoting-effect-of-radiation-on-glucose-metabolism-in-breast-cancer-cells-under-the-treatment-of-cobalt-chloride
#17
Chun-Bo Zhao, Lei Shi, Hai-Hong Pu, Qing-Yuan Zhang
We aimed to investigate the influence of radiation on hypoxia-treated breast cancers cells and its underlying mechanism. We mimicked the hypoxic response in MCF-7 cells by the treatment of CoCl2. Meanwhile, hypoxic MCF-7 cells induced by CoCl2 or untreated MCF-7 cells were treated with or without radiation, and then treated with or without hypoxia inducible factors-1α (HIF-1α) inhibitor. Subsequently, glucose update and lactate release rate were determined by commercial kits, as well as the expressions of HIF-1α and the glucose metabolic pathway related genes, including fructose biphoshatase 1 (FBP1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and isocitrate dehydrogenase 2 (IDH20) were detected by western blotting and/or RT-PCR...
June 24, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27287256/the-lncrna-malat1-acting-through-hif-1%C3%AE-stabilization-enhances-arsenite-induced-glycolysis-in-human-hepatic-l-02-cells
#18
Fei Luo, Xinlu Liu, Min Ling, Lu Lu, Le Shi, Xiaolin Lu, Jun Li, Aihua Zhang, Qizhan Liu
Accelerated glycolysis, a common process in tumor cells called the Warburg effect, is associated with various biological phenomena. However, the role of glycolysis induced by arsenite, a well-established human carcinogen, is unknown. Long non-coding RNAs (lncRNAs) act as regulators in various cancers, but how lncRNAs regulate glucose metabolism remains largely unexplored. We have found that, in human hepatic epithelial (L-02) cells, arsenite increases lactate production; glucose consumption; and expression of glycolysis-related genes, including HK-2, Eno-1, and Glut-4...
September 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27239113/wortmannin-influences-hypoxia-inducible-factor-1-alpha-expression-and-glycolysis-in-esophageal-carcinoma-cells
#19
Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu
AIM: To investigate the influence of phosphatidylinositol-3-kinase protein kinase B (PI3K/AKT)-HIF-1α signaling pathway on glycolysis in esophageal carcinoma cells under hypoxia. METHODS: Esophageal carcinoma cell lines Eca109 and TE13 were cultured under hypoxia environment, and the protein, mRNA and activity levels of hypoxia inducible factor-1 alpha (HIF-1α), glucose transporter 1, hexokinase-II, phosphofructokinase 2 and lactate dehydrogenase-A were determined...
May 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27231905/role-of-mitochondrial-dna-copy-number-alteration-in-human-renal-cell-carcinoma
#20
Chen-Sung Lin, Hui-Ting Lee, Ming-Huei Lee, Siao-Cian Pan, Chen-Yeh Ke, Allen Wen-Hsiang Chiu, Yau-Huei Wei
We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively...
May 25, 2016: International Journal of Molecular Sciences
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