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https://www.readbyqxmd.com/read/28708594/hypoxia-favors-myosin-heavy-chain-beta-gene-expression-in-an-hif-1alpha-dependent-manner
#1
Lucia Binó, Jiřina Procházková, Katarzyna Anna Radaszkiewicz, Jan Kučera, Jana Kudová, Jiří Pacherník, Lukáš Kubala
The potentiation of the naturally limited regenerative capacity of the heart is dependent on an understanding of the mechanisms that are activated in response to pathological conditions such as hypoxia. Under these conditions, the expression of genes suggested to support cardiomyocyte survival and heart adaptation is triggered. Particularly important are changes in the expression of myosin heavy chain (MHC) isoforms. We propose here that alterations in the expression profiles of MHC genes are induced in response to hypoxia and are primarily mediated by hypoxia inducible factor (HIF)...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697344/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#2
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Sarkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28689265/aerobic-glycolysis-hypothesis-through-wnt-beta-catenin-pathway-in-exudative-age-related-macular-degeneration
#3
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)...
July 8, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28686658/a-hypoxia-response-element-in-the-vegfa-promoter-is-required-for-basal-vegfa-expression-in-skin-and-for-optimal-granulation-tissue-formation-during-wound-healing-in-mice
#4
Domenic Ciarlillo, Christophe Celeste, Peter Carmeliet, Derek Boerboom, Christine Theoret
Hypoxia in skin wounds is thought to contribute to healing through the induction of hypoxia inducible factor-1 (HIF-1). Although HIF-1 can regulate the expression of vascular endothelial growth factor A (Vegfa), whether hypoxia and HIF-1 are required to induce Vegfa expression in the context of wound healing is unknown. To test this hypothesis, we evaluated Vegfa expression and wound healing in mutant mice that lack a functional HIF-1 binding site in the Vegfa promoter. Full-thickness excisional wounds were made using a biopsy punch, left to heal by second intention, and granulation tissue isolated on a time course during healing...
2017: PloS One
https://www.readbyqxmd.com/read/28624453/folic-acid-attenuates-cobalt-chloride-induced-pge2-production-in-huvecs-via-the-no-hif-1alpha-cox-2-pathway
#5
Yuming Liang, Xiaozhou Zhen, Kaiwen Wang, Jing Ma
Prostaglandin E2 (PGE2), an important lipid inflammatory mediator involved in the progression of vascular diseases, can be induced by hypoxia in many cell types. While folic acid has been shown to protect against inflammation in THP-1 cells during hypoxia and hypoxia-induced endothelial cell injury, whether it might do so by attenuating PGE2 production remains unclear. To investigate this we constructed a hypoxia-induced injury model by treating human umbilical vein endothelial cells (HUVECs) with cobalt chloride (CoCl2), which mimics the effects of hypoxia...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28619363/acute-hypoxic-stress-effect-on-blood-parameters-antioxidant-enzymes-and-expression-of-hif-1alpha-and-glut-1-genes-in-largemouth-bass-micropterus-salmoides
#6
S Yang, T Yan, H Wu, Q Xiao, H M Fu, J Luo, J Zhou, L L Zhao, Y Wang, S Y Yang, J L Sun, X Ye, S J Li
Dissolved oxygen (DO) plays a crucial role in survival, growth, and normal physiological functions of aquatic organisms. Nevertheless, the mechanisms involved in hypoxic stress and adaptation have not been fully elucidated in Largemouth bass (Micropterus salmoides). To reveal the effect of acute hypoxia on Largemouth bass, we simulated acute hypoxia (DO: 1.2 ± 0.2 mg/L) in the laboratory and analyzed physiological parameters (RBCs, Hb, SOD, CAT, NA(+)/K(+)-ATPase, GPx, and MDA) and gene expression (HIF-1alpha and GLUT-1) in Largemouth bass exposed to various durations of acute hypoxia (0, 1, 2, 4, 8, 12, and 24 h)...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28585205/adipose-tissue-hypoxia-in-obesity-and-its-impact-on-preadipocytes-and-macrophages-hypoxia-hypothesis
#7
Atilla Engin
Obese subjects exhibit lower adipose tissue oxygen consumption in accordance with the lower adipose tissue blood flow. Thus, compared with lean subjects, obese subjects have 44% lower capillary density and 58% lower vascular endothelial growth factor (VEGF). The VEGF expression together with hypoxia-inducible transcription factor-1 (HIF-1) activity also requires phosphatidylinositol 3-kinase (PI3K)- and target of rapamycin (TOR)-mediated signaling. HIF-1alpha is an important signaling molecule for hypoxia to induce the inflammatory responses...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28566998/relative-contribution-of-prolyl-hydroxylase-dependent-and-independent-degradation-of-hif-1alpha-by-proteasomal-pathways-in-cerebral-ischemia
#8
Yomna Badawi, Honglian Shi
Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia and can determine the fate of brain cells during ischemia. However, the mechanism of HIF-1 regulation is still not fully understood in ischemic brains. We tested a hypothesis that both the 26S and the 20S proteasomal pathways were involved in HIF-1α degradation under ischemic conditions. Using in vitro ischemic model (oxygen and glucose deprivation) and a mouse model of middle cerebral artery occlusion, we tested effects of inhibitors of proteasomes and prolyl hydroxylase (PHD) on HIF-1α stability and brain injury in cerebral ischemia...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28386604/hypoxia-determines-survival-outcomes-of-bacterial-infection-through-hif-1alpha-dependent-re-programming-of-leukocyte-metabolism
#9
A A R Thompson, R S Dickinson, F Murphy, J P Thomson, H M Marriott, A Tavares, J Willson, L Williams, A Lewis, A Mirchandani, P Dos Santos Coelho, C Doherty, E Ryan, E Watts, N M Morton, S Forbes, R H Stimson, A G Hameed, N Arnold, J A Preston, A Lawrie, V Finisguerra, M Mazzone, P Sadiku, J Goveia, F Taverna, P Carmeliet, S J Foster, E R Chilvers, A S Cowburn, D H Dockrell, R S Johnson, R R Meehan, M K B Whyte, S R Walmsley
Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes...
February 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28330872/nadph-oxidase-1-supports-proliferation-of-colon-cancer-cells-by-modulating-reactive-oxygen-species-dependent-signal-transduction
#10
Agnes Juhasz, Susan Markel, Shikha Gaur, Han Liu, Jiamo Lu, Guojian Jiang, Xiwei Wu, Smitha Antony, Yongzhong Wu, Giovanni Melillo, Jennifer L Meitzler, Diana C Haines, Donna Butcher, Krishnendu Roy, James H Doroshow
Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates O2(̇̄), is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-%C3%AE-5%C3%AE-1-receptor-expression-in-breast-cancer-to-promote-metastasis
#11
Julia A Ju, Inês Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
Metastasis is the leading cause of breast cancer mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM-binding receptors in this process was explored. Using a bioinformatics approach, the expression of all integrin receptor subunits, in two independent breast cancer patient datasets, were analyzed to determine whether integrin status correlates with a validated hypoxia-inducible gene signature...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28071583/anticancer-activities-of-new-n-hetaryl-2-cyanoacetamide-derivatives-incorporating-4-5-6-7-tetrahydrobenzo-b-thiophene-moiety
#12
Magda F Mohamed, Yasmin M Attia, Samia A Shouman, Ismail A Abdelhamid
Novel series of N-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives are synthesized. The structure of these compounds was elucidated using different spectral tools. Compounds were evaluated for their cytotoxic activities against different types of human cancer cell lines including, breast (MCF-7, T47D, MDA MB231); liver (HEPG-2); colon (HCT116); prostate (PC3); and cervix (HELA) cells. In this study, we used compounds 11 and 12 that showed the highest cytotoxicity on PC3 and HEPG2 cells, to explore their effects on apoptosis, invasion ampamp; metastasis and angiogenesis...
January 10, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27982675/differential-responsiveness-in-vegf-receptor-subtypes-to-hypoxic-stress-in-various-tissues-of-plateau-animals
#13
Hui-Chun Xie, Jin-Gang Li, Jian-Ping He
With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress...
May 4, 2017: Physiological Research
https://www.readbyqxmd.com/read/27845876/hypoxia-induced-microrna-146a-represses-bcl-2-through-traf6-irak1-but-not-smad4-to-promote-chondrocyte-autophagy
#14
Guanghui Chen, Xin Gao, Jing Wang, Cheng Yang, Yang Wang, Yonggang Liu, Weiwei Zou, Tielong Liu
It has been shown that hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1α, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in a hypoxic environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4...
April 1, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27836247/implication-of-vhl-erk5-and-hif-1alpha-in-clear-cell-renal-cell-carcinoma-molecular-basis
#15
Leticia Serrano-Oviedo, José M Giménez-Bachs, Syongh Y Nam-Cha, Francisco J Cimas, Jesús García-Cano, Ricardo Sánchez-Prieto, Antonio S Salinas-Sánchez
OBJECTIVES: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. MATERIAL AND METHODS: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables...
March 2017: Urologic Oncology
https://www.readbyqxmd.com/read/27742687/lysyl-oxidase-is-a-strong-determinant-of-tumor-cell-colonization-in-bone
#16
Caroline Reynaud, Laura Ferreras, Paola Di Mauro, Casina Kan, Martine Croset, Edith Bonnelye, Floriane Pez, Clémence Thomas, Géraldine Aimond, Antoine E Karnoub, Marie Brevet, Philippe Clézardin
Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase whose primary function is to drive collagen crosslinking and extracellular matrix stiffness. LOX in colorectal cancer synergizes with hypoxia-inducible factor-1 (HIF-1) to promote tumor progression. Here we investigated whether LOX/HIF1 endows colorectal cancer cells with full competence for aggressive colonization in bone. We show that a high LOX expression in primary tumors from patients with colorectal cancer was associated with poor clinical outcome, irrespective of HIF-1 In addition, LOX was expressed by tumor cells in the bone marrow from colorectal cancer patients with bone metastases...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27601067/melatonin-promotes-cardiomyogenesis-of-embryonic-stem-cells-via-inhibition-of-hif-1%C3%AE-stabilization
#17
Jana Kudová, Ondřej Vašíček, Milan Číž, Lukáš Kubala
Melatonin, a molecule involved in the regulation of circadian rhythms, has protective effects against myocardial injuries. However, its capability to regulate the maturation of cardiac progenitor cells is unclear. Recently, several studies have shown that melatonin inhibits the stabilization of hypoxia-inducible factors (HIFs), important signaling molecules with cardioprotective effects. In this study, by employing differentiating mouse embryonic stem cells, we report that melatonin significantly upregulated the expression of cardiac cell-specific markers (myosin heavy chains six and seven) as well as the percentage of myosin heavy chain-positive cells...
November 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27355368/hif-1alpha-deficiency-attenuates-the-cardiomyogenesis-of-mouse-embryonic-stem-cells
#18
Jana Kudová, Jiřina Procházková, Ondřej Vašiček, Tomáš Perečko, Miroslava Sedláčková, Martin Pešl, Jiří Pacherník, Lukáš Kubala
Cardiac cell formation, cardiomyogenesis, is critically dependent on oxygen availability. It is known that hypoxia, a reduced oxygen level, modulates the in vitro differentiation of pluripotent cells into cardiomyocytes via hypoxia inducible factor-1alpha (HIF-1α)-dependent mechanisms. However, the direct impact of HIF-1α deficiency on the formation and maturation of cardiac-like cells derived from mouse embryonic stem cells (mESC) in vitro remains to be elucidated. In the present study, we demonstrated that HIF-1α deficiency significantly altered the quality and quantity of mESC-derived cardiomyocytes...
2016: PloS One
https://www.readbyqxmd.com/read/27253378/lipid-albumin-nanoparticles-lan-for-therapeutic-delivery-of-antisense-oligonucleotide-against-hif-1%C3%AE
#19
Hong Li, Jishan Quan, Mengzi Zhang, Bryant C Yung, Xinwei Cheng, Yang Liu, Young B Lee, Chang-Ho Ahn, Deog Joong Kim, Robert J Lee
Lipid-albumin nanoparticles (LAN) were synthesized for delivery of RX-0047, an antisense oligonucleotide (ASO) against the hypoxia inducible factor-1 alpha (HIF-1α) to solid tumor. These lipid nanoparticles (LNs) incorporated a human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate, which is cationic and can form electrostatic complexes with negatively charged oligonucleotides. The delivery efficiency of LAN-RX-0047 was investigated in KB cells and a KB murine xenograft model. When KB cells were treated with LAN-RX-0047, significant HIF-1α downregulation and enhanced cellular uptake were observed compared to LN-RX-0047...
July 5, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27102266/dual-time-point-fdg-pet-ct-and-fdg-uptake-and-related-enzymes-in-lymphadenopathies-preliminary-results
#20
Sofie Bæk Christlieb, Casper Nørgaard Strandholdt, Birgitte Brinkmann Olsen, Karen Juul Mylam, Thomas Stauffer Larsen, Anne Lerberg Nielsen, Max Rohde, Oke Gerke, Karen Ege Olsen, Michael Boe Møller, Bjarne Winther Kristensen, Niels Abildgaard, Abass Alavi, Poul Flemming Høilund-Carlsen
PURPOSE: The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with (18)F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed. METHODS: Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration)...
September 2016: European Journal of Nuclear Medicine and Molecular Imaging
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