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Lactate AND HIF-1

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https://www.readbyqxmd.com/read/29413596/an-aptamer-fe3-modified-nanoparticle-for-lactate-oxidation-and-tumor-photodynamic-therapy
#1
Huan Yang, Wen-Long Lu, Tao Huang, Qiu-Yun Chen, Jing Gao, Yao Zhao
To develop a cancer targeting lactate attenuator in vivo for cancer phototherapy and inhibition of HIF-1, we report an aptamer modified photo-responsive nanoparticle (labeled as Mn-D@BPFe-A) for lactate oxidation and cancer phototherapy. Mn-D@BPFe-A was constructed by the assembly of functional complex with BSA, followed by surface metal coordination and the recognition of Fe3+ with GAG containing sequence. Upon irradiation, Mn-D@BPFe-A NPs can oxidize water with the generation of OH, which convert lactate into pyruvate both in vitro and in vivo...
January 29, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29365089/stat5-dependent-cardioprotection-in-late-remote-ischemia-preconditioning
#2
Hui Chen, Xin-Yue Jing, Yu-Jun Shen, Tian-Lin Wang, Chen Ou, Sheng-Feng Lu, Yun Cai, Qian Li, Ya-Juan Ding, Xiao-Chun Yu, Bing-Mei Zhu
Aims: To study the protective effects of late remote ischemic preconditioning (RIPC) against myocardial ischemia/reperfusion (I/R) injury and determine whether Stat5 is involved in this protection by using cardiomyocyte-specific Stat5 knockout mice (Stat5-cKO). Methods and results: Mice were exposed to lower limb RIPC or sham ischemia. After 24 hours, the left anterior descending artery (LAD) was ligated for 30 minutes, then reperfused for 180 minutes. The myocardial infarct size, apoptotic rate of cardiomyocytes, and serum myocardial enzymes were measured to evaluate for cardioprotective effects...
January 22, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29356574/pyruvate-kinase-m2-modulates-the-glycolysis-of-chondrocyte-and-extracellular-matrix-in-osteoarthritis
#3
Xiaobo Yang, Weiping Chen, Xiang Zhao, Linwei Chen, Wanli Li, Jisheng Ran, Lidong Wu
Pyruvate kinase M2 (PKM2) has been wildly verified to modulate glycolysis in tumor cells. However, the role of PKM2 on the glycolysis of osteoarthritis (OA) chondrocytes is still unclear. In present study, we investigate the function of PKM2 on OA chondrocyte glycolysis and the collagen matrix generation in vitro. Results showed that PKM2 was upregulated in OA chondrocytes compared with healthy control chondrocytes. In OA chondrocytes, ATP expression was lower compared with healthy control chondrocytes. Loss-of-function experiment showed that PKM2 knockdown mediated by lentivirus transfection could significantly suppress the glucose consumption and lactate secretion levels and decrease glucose transporter-1 (Glut-1), lactate dehydrogenase A (LDHA), and hypoxia inducible factor 1-alpha (HIF-1α), indicating the inhibition of PKM2 knockdown on glycolysis...
January 22, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29337249/regulation-of-lactate-dehydrogenase-in-response-to-wssv-infection-in-the-shrimp-litopenaeus-vannamei
#4
M L E Hernández-Palomares, J A Godoy-Lugo, S Gómez-Jiménez, L A Gámez-Alejo, R M Ortiz, J F Muñoz-Valle, A B Peregrino-Uriarte, G Yepiz-Plascencia, J A Rosas-Rodríguez, J G Soñanez-Organis
Lactate dehydrogenase (LDH) is key for anaerobic glycolysis. LDH is induced by the hypoxia inducible factor -1 (HIF-1). HIF-1 induces genes involved in glucose metabolism and regulates cellular oxygen homeostasis. HIF-1 is formed by a regulatory α-subunit (HIF-1α) and a constitutive β-subunit (HIF-1β). The white spot syndrome virus (WSSV) induces anaerobic glycolysis in shrimp hemocytes, associated with lactate accumulation. Although infection and lactate production are associated, the LDH role in WSSV-infected shrimp has not been examined...
January 11, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29207023/macrophage-migration-inhibitory-factor-promotes-warburg-effect-via-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-hif%C3%A2-1%C3%AE-pathway-in-lung-cancer
#5
Jun Li, Junhua Zhang, Fengjiao Xie, Jiangzhou Peng, Xu Wu
Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA...
February 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29190880/enhancement-of-the-anti-tumor-activity-of-fgfr1-inhibition-in-squamous-cell-lung-cancer-by-targeting-downstream-signaling-involved-in-glucose-metabolism
#6
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...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158891/overexpression-of-hypoxia-inducible-factor-and-metabolic-pathways-possible-targets-of-cancer
#7
REVIEW
Davinder Singh, Rohit Arora, Pardeep Kaur, Balbir Singh, Rahul Mannan, Saroj Arora
Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29100428/lactate-stimulates-ca-ix-expression-in-normoxic-cancer-cells
#8
Elena Panisova, Martin Kery, Olga Sedlakova, Lucie Brisson, Michaela Debreova, Martina Sboarina, Pierre Sonveaux, Silvia Pastorekova, Eliska Svastova
Besides hypoxia, other factors and molecules such as lactate, succinate, and reactive oxygen species activate transcription factor hypoxia-inducible factor-1 (HIF-1) even in normoxia. One of the main target gene products of HIF-1 is carbonic anhydrase IX (CA IX). CA IX is overexpressed in many tumors and serves as prognostic factor for hypoxic, aggressive and malignant cancers. CA IX is also induced in normoxia in high cell density. In this study, we observed that lactate induces CA IX expression in normoxic cancer cells in vitro and in vivo...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28991527/mangiferin-ameliorates-insulin-resistance-by-inhibiting-inflammation-and-regulatiing-adipokine-expression-in-adipocytes-under-hypoxic-condition
#9
Chao-Qiang Yang, Jing-Hua Xu, Dan-Dan Yan, Bao-Lin Liu, Kang Liu, Fang Huang
Adipose tissue hypoxia has been recognized as the initiation of insulin resistance syndromes. The aim of the present study was to investigate the effects of mangiferin on the insulin signaling pathway and explore whether mangiferin could ameliorate insulin resistance caused by hypoxia in adipose tissue. Differentiated 3T3-L1 adipocytes were incubated under normal and hypoxic conditions, respectively. Protein expressions were analyzed by Western blotting. Inflammatory cytokines and HIF-1-dependent genes were tested by ELISA and q-PCR, respectively...
September 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28940640/bicarbonate-recycling-by-hif-1-dependent-carbonic-anhydrase-isoforms-9-and-12-is-critical-in-maintaining-intracellular-ph-and-viability-of-nucleus-pulposus-cells
#10
Elizabeth S Silagi, Zachary R Schoepflin, Erin L Seifert, Christophe Merceron, Ernestina Schipani, Irving M Shapiro, Makarand V Risbud
Intervertebral disc degeneration is a ubiquitous condition closely linked to chronic low-back pain. The health of the avascular nucleus pulposus (NP) plays a crucial role in the development of this pathology. We tested the hypothesis that a network comprising HIF-1α, Carbonic anhydrase (CA) 9 and 12 isoforms, and sodium-coupled bicarbonate cotransporters (NBCs) buffer intracellular pH through coordinated bicarbonate recycling. Contrary to the current understanding of NP cell metabolism, analysis of metabolic-flux data from Seahorse XF analyzer showed that CO2 hydration contributes a significant source of extracellular proton production in NP cells, with a smaller input from glycolysis...
September 23, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28926527/genistein-suppresses-aerobic-glycolysis-and-induces-hepatocellular-carcinoma-cell-death
#11
Sainan Li, Jingjing Li, Weiqi Dai, Qinghui Zhang, Jiao Feng, Liwei Wu, Tong Liu, Qiang Yu, Shizan Xu, Wenwen Wang, Xiya Lu, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Xiaoming Fan, Wenhui Mo, Ling Xu, Chuanyong Guo
BACKGROUND: Genistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear. METHODS: Cell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation...
November 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28886081/orexin-a-affects-hepg2-human-hepatocellular-carcinoma-cells-glucose-metabolism-via-hif-1%C3%AE-dependent-and-independent-mechanism
#12
Xing Wan, Yuanyuan Liu, Yuyan Zhao, Xiaoqi Sun, Dongxiao Fan, Lei Guo
Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28879655/pretreatment-with-fish-oil-attenuates-heart-ischaemia-consequences-in-rats
#13
Alcione Lescano de Souza Junior, Jorge Mancini Filho, Rosângela Pavan Torres, Maria Cláudia Irigoyen, Rui Curi
What is the central question of this study? We investigated whether pretreatment with fish oil could prevent the major consequences of ischaemic injury to the heart. What is the main finding and its importance? Fish oil pretreatment attenuated the consequences of ischaemic injury as indicated by the small infarction area and the preservation of systolic function and coronary blood flow. These findings support the use of fish oil in order to reduce the impact of heart ischaemia. ω-3 Polyunsaturated fatty acid (ω-3 PUFA)-rich fish oil supplementation has protective effects on heart ischaemic injury...
September 6, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28857035/two-common-variants-of-human-papillomavirus-type-16-e6-differentially-deregulate-sugar-metabolism-and-hypoxia-signalling-in-permissive-human-keratinocytes
#14
Sean Cuninghame, Robert Jackson, Simon J Lees, Ingeborg Zehbe
Human papillomavirus type 16 (HPV16) is responsible for most cancers attributable to HPV infection and naturally occurring variants of the HPV16 E6 oncoprotein predispose individuals to varying risk for developing cancer. Population studies by us and others have demonstrated that the common Asian-American E6 (AAE6) variant is a higher risk factor for cervical cancer than the E6 of another common variant, the European prototype (EPE6). However, a complete understanding of the molecular processes fundamental to these epidemiological findings is still lacking...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28828258/the-key-role-of-microtubules-in-hypoxia-preconditioning-induced-nuclear-translocation-of-hif-1%C3%AE-in-rat-cardiomyocytes
#15
Hai Guo, Hong Zheng, Jianjiang Wu, Hai-Ping Ma, Jin Yu, Maimaitili Yiliyaer
BACKGROUND: Hypoxia-inducible factor (HIF)-1 is involved in the regulation of hypoxic preconditioning in cardiomyocytes. Under hypoxic conditions, HIF-1α accumulates and is translocated to the nucleus, where it forms an active complex with HIF-1β and activates transcription of approximately 60 kinds of hypoxia-adaptive genes. Microtubules are hollow tubular structures in the cell that maintain cellular morphology and that transport substances. This study attempted to clarify the role of microtubule structure in the endonuclear aggregation of HIF-1α following hypoxic preconditioning of cardiomyocytes...
2017: PeerJ
https://www.readbyqxmd.com/read/28827059/enhanced-aerobic-glycolysis-of-nasopharyngeal-carcinoma-cells-by-epstein-barr-virus-latent-membrane-protein-1
#16
Wei-Wen Sung, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells...
October 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#17
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
#18
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 tumors, characteristics that contribute to the poor prognosis associated with this type of tumor. A lactate shuttle has been described between tumor cells and endothelial cells (ECs), with the monocarboxylate transporters (MCTs) acting as important players in this tumor-EC communication. In this study, we aimed to understand how the tumor 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
#19
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
#20
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...
November 15, 2017: International Journal of Cancer. Journal International du Cancer
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