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hypoxic transcription factor

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https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#1
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#2
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29136509/an-hif-1%C3%AE-vegf-a-axis-in-cytotoxic-t-cells-regulates-tumor-progression
#3
Asis Palazon, Petros A Tyrakis, David Macias, Pedro Veliça, Helene Rundqvist, Susan Fitzpatrick, Nikola Vojnovic, Anthony T Phan, Niklas Loman, Ingrid Hedenfalk, Thomas Hatschek, John Lövrot, Theodoros Foukakis, Ananda W Goldrath, Jonas Bergh, Randall S Johnson
Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation to the hypoxic tumor microenvironment. Deletion analyses of the two key HIF isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8(+) T cells. Furthermore, loss of HIF-1α in CD8(+) T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, an HIF target gene, in CD8(+) T cells accelerated tumorigenesis while also altering vascularization...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29129785/advances-in-hypoxia-inducible-factor-biology
#4
REVIEW
Hani Choudhry, Adrian L Harris
Hypoxia-inducible factor (HIF), a central regulator for detecting and adapting to cellular oxygen levels, transcriptionally activates genes modulating oxygen homeostasis and metabolic activation. Beyond this, HIF influences many other processes. Hypoxia, in part through HIF-dependent mechanisms, influences epigenetic factors, including DNA methylation and histone acetylation, which modulate hypoxia-responsive gene expression in cells. Hypoxia profoundly affects expression of many noncoding RNAs classes that have clinicopathological implications in cancer...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29127200/steroid-receptor-coactivator-2-src-2-coordinates-cardiomyocyte-paracrine-signaling-to-promote-pressure-overload-induced-angiogenesis
#5
Ji Ho Suh, Li Lai, Deokhwa Nam, Jong Kim, Juyeon Jo, George E Taffet, Eunah Kim, Jason T Kaelber, Hyun-Kyoung Lee, Mark L Entman, John P Cooke, Erin L Reineke
Pressure overload-induced cardiac stress induces left ventricular hypertrophy driven by increased cardiomyocyte mass. The increased energetic demand and cardiomyocyte size during hypertrophy necessitate increased fuel and oxygen delivery and stimulate angiogenesis in the left ventricular wall. We have previously shown that the transcriptional regulator steroid receptor coactivator-2 (SRC-2) controls activation of several key cardiac transcription factors and that SRC-2 loss results in extensive cardiac transcriptional remodeling...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29117182/structural-and-functional-analysis-of-coral-hypoxia-inducible-factor
#6
Didier Zoccola, Jonas Morain, Gilles Pagès, Natacha Caminiti-Segonds, Sandy Giuliano, Sylvie Tambutté, Denis Allemand
Tissues of symbiotic Cnidarians are exposed to wide, rapid and daily variations of oxygen concentration. Indeed, during daytime, intracellular O2 concentration increases due to symbiont photosynthesis, while during night, respiration of both host cells and symbionts leads to intra-tissue hypoxia. The Hypoxia Inducible Factor 1 (HIF-1) is a heterodimeric transcription factor used for maintenance of oxygen homeostasis and adaptation to hypoxia. Here, we carried out a mechanistic study of the response to variations of O2 concentrations of the coral model Stylophora pistillata...
2017: PloS One
https://www.readbyqxmd.com/read/29115598/effects-of-hypoxia%C3%A2-inducible-factor%C3%A2-1%C3%AE-on-endometrial-receptivity-of-women-with-polycystic-ovary-syndrome
#7
Dongmei Zhao, Qinglan Qu, Huangguan Dai, Yueyang Liu, Lei Jiang, Xin Huang, Cuifang Hao
Embryo implantation is associated with an hypoxic endometrial microenvironment. Hypoxia‑inducible factor‑1α (HIF‑1α) is activated under hypoxic conditions. In the present study, the expression pattern of HIF‑1α in endometrial tissue was investigated and its effects on endometrial receptivity in patients with polycystic ovary syndrome (PCOS) were examined. A total of 81 patients were enrolled for in vitro fertilization and embryo transfer. They were divided into PCOS (n=40) and Control groups (n=41); both groups were further divided based on body weight (overweight and normal weight subgroups)...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29112674/interleukin-10-and-pd150606-modulate-expression-of-ampa-receptor-glua1-and-glua2-subunits-under-hypoxic-conditions
#8
Sergei G Levin, Nikolai P Sirota, Miroslav N Nenov, Tatyana A Savina, Oleg V Godukhin
The goal of this study was to evaluate the effects of anti-inflammatory cytokine, interleukin-10 (IL-10), and calpain inhibitor, PD150606, on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits in rat hippocampal slices exposed to repeated brief hypoxic episodes. We studied both individual and combinatory effects of PD150606 and IL-10 on the expression of AMPA receptor subunits under hypoxic conditions for GluA1 and GluA2 as well as their phosphorylated forms - pSer831-GluA1 and pSer880-GluA2...
November 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/29108235/regulation-of-sirt3-signal-related-metabolic-reprogramming-in-gastric-cancer-by-helicobacter-pylori-oncoprotein-caga
#9
Do Yeon Lee, Dawoon E Jung, Sung Sook Yu, Yeo Song Lee, Beom Ku Choi, Yong Chan Lee
Injection of the Helicobacter pylori cytotoxin-associated gene A (CagA) is closely associated with the development of chronic gastritis and gastric cancer. Individuals infected with H. pylori possessing the CagA protein produce more reactive oxygen species (ROS) and show an increased risk of developing gastric cancer. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases and mitochondrial SIRT3 is known to be a tumor suppressor via its ability to suppress ROS and hypoxia inducible factor 1α (HIF-1α)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106390/glycolysis-gatekeeper-pdk1-reprograms-breast-cancer-stem-cells-under-hypoxia
#10
F Peng, J-H Wang, W-J Fan, Y-T Meng, M-M Li, T-T Li, B Cui, H-F Wang, Y Zhao, F An, T Guo, X-F Liu, L Zhang, L Lv, D-K Lv, L-Z Xu, J-J Xie, W-X Lin, E W-F Lam, J Xu, Q Liu
Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH(+) subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival...
November 6, 2017: Oncogene
https://www.readbyqxmd.com/read/29100428/lactate-stimulates-ca-ix-expression-in-normoxic-cancer-cells
#11
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/29100106/l-mimosine-and-hypoxia-enhance-angiopoietin-like-4-production-involving-hypoxia-inducible-factor-1alpha-insights-from-monolayer-and-spheroid-cultures-of-dental-pulp-derived-cells-and-tooth-slice-cultures
#12
Klara Janjić, Umar Alhujazy, Andreas Moritz, Hermann Agis
OBJECTIVE: Angiopoietin-like 4 (Angptl4) is an angiogenesis modulating signaling factor and as such involved in blood vessel formation but also in hard tissue resorption. Here we hypothesized that the hypoxia mimetic agent L-mimosine (L-MIM) and hypoxia stimulate the production of Angptl4 in the dental pulp. MATERIAL AND METHODS: Monolayer and spheroid cultures of primary human dental pulp-derived cells (DPC) were treated with L-MIM or hypoxia. Furthermore, tooth slice cultures were performed...
October 16, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29083304/prolyl-dihydroxylation-of-unassembled-us12-rps23-regulates-fungal-hypoxic-adaptation
#13
Sara J Clasen, Wei Shao, He Gu, Peter Espenshade
The prolyl-3,4-dihydroxylase Ofd1 and nuclear import adaptor Nro1 regulate the hypoxic response in fission yeast by controlling activity of the sterol regulatory element-binding protein transcription factor Sre1. Here, we identify an extra-ribosomal function for uS12/Rps23 central to this regulatory system. Nro1 binds Rps23, and Ofd1 dihydroxylates Rps23 P62 in complex with Nro1. Concurrently, Nro1 imports Rps23 into the nucleus for assembly into 40S ribosomes. Low oxygen inhibits Ofd1 hydroxylase activity and stabilizes the Ofd1-Rps23-Nro1 complex, thereby sequestering Ofd1 from binding Sre1, which is then free to activate hypoxic gene expression...
October 30, 2017: ELife
https://www.readbyqxmd.com/read/29078168/stat3-rxr-nrf2-activates-systemic-redox-and-energy-homeostasis-upon-steep-decline-in-po2-gradient
#14
Subhojit Paul, Anamika Gangwar, Kalpana Bhargava, Yasmin Ahmad
Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and propose a model for rapid acclimatization of high altitude visitors to enhance their performance based on molecular changes...
October 17, 2017: Redox Biology
https://www.readbyqxmd.com/read/29075670/melanoma-topology-reveals-a-stem-like-phenotype-that-promotes-angiogenesis
#15
Junmin Lee, Amr A Abdeen, Jamila Hedhli, Kathryn L Wycislo, Iwona T Dobrucka, Timothy M Fan, Lawrence W Dobrucki, Kristopher A Kilian
Tumor angiogenesis provides critical nutrients for cancer progression and may also facilitate pathways for dissemination during the process of metastasis. It is well established that cells that metastasize display characteristics of stem cells; however, the prevailing paradigm points to these stem-like cells residing in the hypoxic niche within the tumor interior. Controlling the geometry at the interface of a population of melanoma cells reveals a role for perimeter topology in promoting a stem-like state with enhanced tumorigenicity...
October 2017: Science Advances
https://www.readbyqxmd.com/read/29074702/respiratory-consequences-of-targeted-losses-of-hoxa5-gene-function-in-mice
#16
Kim Landry-Truchon, Stéphanie Fournier, Nicolas Houde, Jean-Philippe Rousseau, Lucie Jeannotte, Richard Kinkead
Fetal development of the respiratory tract and diaphragm requires strict coordination between genetically controlled signals and mechanical forces produced by the neural network that generates breathing. Being expressed in the mesenchyme of trachea, lung and diaphragm, and in phrenic motoneurons HOXA5 is a key transcription factor regulating lung development and function. Consequently, most Hoxa5(-/-) mutants die at birth from respiratory failure. However, the extensive effect of the null mutation makes it difficult to identify the origins of respiratory dysfunction in newborns...
October 26, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29067112/bone-marrow-mesenchymal-stem-cells-repair-the-hippocampal-neurons-and-increase-the-expression-of-igf-1-after-cardiac-arrest-in-rats
#17
Xiahong Tang, Feng Chen, Qinming Lin, Yan You, Jun Ke, Shen Zhao
The present study aimed to investigate the beneficial effects and underlying mechanisms of bone marrow mesenchymal stem cells (BMSCs) on global ischemic hypoxic brain injury. Cells collected from the femurs and tibias of male Sprague Dawley rats were used to generate BMSCs following three culture passages. A rate model of cardiac arrest (CA) was induced by asphyxia. One hour following return of spontaneous circulation (ROSC), BMSCs were transplanted through injection into the tail vein. Neurological status was assessed using modified neurological severity score (mNSS) tests 1, 3 and 7 days following ROSC...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29065407/hypoxic-stress-upregulates-the-expression-of-slc38a1-in-brown-adipocytes-via-hypoxia-inducible-factor-1%C3%AE
#18
Tetsuhiro Horie, Kazuya Fukasawa, Takashi Iezaki, Gyujin Park, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Eiichi Hinoi
The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro...
October 25, 2017: Pharmacology
https://www.readbyqxmd.com/read/29063737/allogeneic-stem-cells-alter-gene-expression-and-improve-healing-of-distal-limb-wounds-in-horses
#19
Jamie A Textor, Kaitlin C Clark, Naomi J Walker, Fabio A Aristizobal, Amir Kol, Sarah S LeJeune, Andrea Bledsoe, Arik Davidyan, Sarah N Gray, Laurie K Bohannon-Worsley, Kevin D Woolard, Dori L Borjesson
Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed...
October 24, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29059701/interferon-regulatory-factor-1-rab27a-regulated-extracellular-vesicles-promote-liver-ischemia-reperfusion-injury
#20
Mu-Qing Yang, Qiang Du, Julie Goswami, Patrick R Varley, Bin Chen, Rong-Hua Wang, Adrian E Morelli, Donna B Stolz, Timothy R Billiar, Jiyu Li, David A Geller
The role and regulators of extracellular vesicles (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a GTPase known to control EVs release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain GTPases. However, the relationships among IRF-1, Rab27a, and EVs secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers...
October 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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