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Hypoxia induced factor

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https://www.readbyqxmd.com/read/28723626/positive-correlation-of-cg16672562-methylation-with-obesity-related-traits-in-childhood-obesity-and-its-independence-with-underlying-hif3a-hypoxia-inducible-factor-3a-genetic-background
#1
Suman Lee, Hyo Jin Kim, Sohee Han, Jae-Pil Jeon, Sang-Ick Park, Ho-Yeong Yu, Mi Yeong Hwang, Juyoung Lee
Differential methylations of the HIF3A (hypoxia-inducible factor 3a) gene have been linked to body mass index (BMI). To explore the association of these methylations to childhood obesity, we measured 5 CpG methylation sites (cg27146050, cg46801562, cg22891070, cg16672562 and cg46801675) in intron 1 of the HIF3A gene by pyrosequencing, in the Korean population (mean age: 13.9 yrs, 305 obese cases and 387 controls). Two CpG methylations, cg46801562 and cg16672562, had statistically significant association with childhood obesity (P = 2...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#2
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28721559/anatomical-specificity-of-the-brain-in-the-modulation-of-neuroglobin-and-cytoglobin-genes-after-chronic-bisphenol-a-exposure
#3
Rodrigo Rodrigues da Conceição, Janaina Sena de Souza, Kelen Carneiro de Oliveira, Rui Monteiro de Barros Maciel, Marco Aurélio Romano, Renata Marino Romano, Magnus Régios Dias da Silva, Maria Izabel Chiamorela, Gisele Giannocco
The aim of this study was to investigate the influence of Bisphenol A (BPA) exposure on Neuroglobin (Ngb) and Cytoglobin (Cygb) as well as oxidative stress gene expression in the cerebellum, hippocampus, hypothalamus and cortex. Male Wistar rats were randomly divided into 3 groups: Control and two groups receiving 2 different daily BPA dosages, 5 or 25 mg/kg from postnatal day 50 (PND50) through PND90 and they were euthanized at PND105. In the cortex, we found an increase in Ngb gene expression and also in superoxide dismutase 1 and Catalase (Cat)...
July 18, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28721162/the-influence-of-rapamycin-on-the-early-cardioprotective-effect-of-hypoxic-preconditioning-on-cardiomyocytes
#4
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/28720497/nrf2-overexpression-in-mesenchymal-stem-cells-induces-stem-cell-marker-expression-and-enhances-osteoblastic-differentiation
#5
Yuan Zenan, Jian Zhang, Huang Yong, Yingcai Zhang, Liu Wei, Wang Genshu, Qi Zhang, Wang Guoying, Yang Yang, Li Hua, Guihua Chen
Hypoxic environment has been suggested in stem cell culturing as their physiologic niche requires oxygen tension to maintain stemness. The administration of cobalt chloride (CoCl2) was widely applied in mimicking hypoxia for its economic advantages and convenience. We confirmed that CoCl2 could maintain stemness and promote the osteogenesis capacity of MSCs. However, CoCl2 could induce the apoptosis and hinder the proliferation of MSCs. To find out a potential method maintaining their stemness without threatening their survival, we analyzed the database of Gene Expression Omnibus (GEO) and proposed that NRF2 (nuclear factor erythroid-derived 2-like 2) might be the potential target...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28720067/hpv16-e6-e7-upregulates-hif-2%C3%AE-and-vegf-by-inhibiting-lkb1-in-lung-cancer-cells
#6
Jian-Shuang Shao, Jian Sun, Shiyu Wang, Katherine Chung, Jin Tong Du, Jason Wang, Xue-Shan Qiu, En-Hua Wang, Guang-Ping Wu
Long-term persistent infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. However, molecular mechanisms of HPV16 E6/E7 induction of lung cancer are not fully understood. Using bi-directional genetic manipulation and four well-established lung cancer cell lines, we showed HPV16 E6/E7 downregulated expression of liver kinase B1 at both protein and messenger RNA levels; liver kinase B1 downregulated hypoxia-inducible factor 2α at protein level but not at messenger RNA level, and hypoxia-inducible factor 2α upregulated vascular endothelial growth factor at both protein and messenger RNA levels...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28718507/gene-expression-analyses-reveal-metabolic-specifications-in-acute-o2-sensing-chemoreceptor-cells
#7
Lin Gao, Victoria Bonilla-Henao, Paula García-Flores, Ignacio Arias-Mayenco, Patricia Ortega-Sáenz, José López-Barneo
Acute O2 sensing is a fundamental property of cells in the peripheral chemoreceptors, e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM), and is necessary for adaptation to hypoxia. These cells contain O2 -sensitive ion channels, which mediate membrane depolarization and transmitter release upon exposure to hypoxia. However, the mechanisms underlying the detection of changes in O2 tension by cells are still poorly understood. Recently, we suggested that CB glomus cells have specific metabolic features that favour the accumulation of reduced quinone and the production of mitochondrial NADH and reactive oxygen species during hypoxia...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28718406/targeting-hypoxia-inducible-factors-for-antiangiogenic-cancer-therapy
#8
REVIEW
Sergio Rey, Luana Schito, Bradly G Wouters, Scott Eliasof, Robert S Kerbel
Hypoxia (low O2) is a pathobiological hallmark of solid cancers, resulting from the imbalance between cellular O2 consumption and availability. Hypoxic cancer cells (CCs) stimulate blood vessel sprouting (angiogenesis), aimed at restoring O2 delivery to the expanding tumor masses through the activation of a transcriptional program mediated by hypoxia-inducible factors (HIFs). Here, we review recent data suggesting that the efficacy of antiangiogenic (AA) therapies is limited in some circumstances by HIF-dependent compensatory responses to increased intratumoral hypoxia...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717592/epas1-variants-in-high-altitude-tibetan-wolves-were-selectively-introgressed-into-highland-dogs
#9
Bridgett vonHoldt, Zhenxin Fan, Diego Ortega-Del Vecchyo, Robert K Wayne
BACKGROUND: Admixture can facilitate adaptation. For example, black wolves have obtained the variant causing black coat color through past hybridization with domestic dogs and have higher fitness than gray colored wolves. Another recent example of the transfer of adaptive variation between the two species has been suggested by the similarity between high altitude Tibetan mastiffs and wolves at the EPAS1 gene, a transcription factor induced in low oxygen environments. METHODS: Here, we investigate the directionality of admixture in EPAS1 between 28 reference highland gray wolves, 15 reference domestic dogs, and 21 putatively admixed highland wolves...
2017: PeerJ
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#10
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28715484/multiple-renal-cancer-susceptibility-polymorphisms-modulate-the-hif-pathway
#11
Steffen Grampp, Virginia Schmid, Rafik Salama, Victoria Lauer, Franziska Kranz, James L Platt, James Smythies, Hani Choudhry, Margarete Goppelt-Struebe, Peter J Ratcliffe, David R Mole, Johannes Schödel
Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28713984/downregulation-of-microrna%C3%A2-199a%C3%A2-5p-protects-cardiomyocytes-in-cyanotic-congenital-heart-disease-by-attenuating-endoplasmic-reticulum-stress
#12
Yang Zhou, Wei-Kun Jia, Zhao Jian, Liang Zhao, Chen-Cheng Liu, Yong Wang, Ying-Bin Xiao
Chronic hypoxia is a key pathological change in patients with cyanotic congenital heart defect (CCHD). It has been demonstrated that enhanced myocardial unfolded protein response (UPR) increases the capacity to buffer endoplasmic reticulum (ER) stress and to avoid subsequent apoptosis caused by the hypoxia that underlies CCHD. The present study was performed to determine the regulatory role of microRNAs (miRNAs) in this cytoprotective UPR process. The results revealed that miR‑199a‑5p was markedly downregulated in the cardiac tissue of patients with CCHD and in human myocardial cells cultured in hypoxic conditions...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713976/melittin-exerts-an-antitumor-effect-on-non%C3%A2-small-cell-lung-cancer-cells
#13
Su-Fang Zhang, Zhe Chen
Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713956/mdg%C3%A2-1-inhibits-h2o2%C3%A2-induced-apoptosis-and-inflammation-in-human-umbilical-vein-endothelial-cells
#14
Luo-Cheng Li, Zhi-Wei Wang, Xiao-Ping Hu, Zhi-Yong Wu, Zhi-Peng Hu, Yong-Le Ruan
MDG‑1, a water‑soluble polysaccharide extracted from Ophiopogon japonicus, has been reported to serve a role in antimyocardial ischemia by protecting cardiomyocytes from hypoxia/reoxygenation‑induced damage. However, it remains unknown whether MDG‑1 protects human umbilical vein endothelial cells (HUVECs) against oxidative stress‑induced damage. In the present study, HUVECs were treated with hydrogen peroxide (H2O2) to establish an oxidative stress‑induced cell injury model. Treatment of HUVECs with different concentrations of H2O2 significantly attenuated cell viability and increased cell apoptosis in a time and dose‑dependent manner...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713640/human-adipose-derived-mesenchymal-stem-cells-respond-to-short-term-hypoxia-by-secreting-factors-beneficial-for-human-islets-in-vitro-and-potentiate-antidiabetic-effect-in-vivo
#15
Simen W Schive, Mohammad Reza Mirlashari, Grete Hasvold, Mengyu Wang, Dag Josefsen, Hans Petter Gullestad, Olle Korsgren, Aksel Foss, Gunnar Kvalheim, Hanne Scholz
Adipose-derived mesenchymal stem cells (ASCs) release factors beneficial for islets in vitro and protect against hyperglycemia in rodent models of diabetes. Oxygen tension has been shown to induce metabolic changes and alter ASCs' release of soluble factors. The effects of hypoxia on the antidiabetic properties of ASCs have not been explored. To investigate this, we incubated human ASCs for 48 h in 21% (normoxia) or 1% O2 (hypoxia) and compared viability, cell growth, surface markers, differentiation capability, and soluble factors in the conditioned media (CM)...
2017: Cell Medicine
https://www.readbyqxmd.com/read/28712399/-expressions-of-stem-cell-factor-and-hypoxia-inducible-factor-1-alpha-in-pancreatic-cancer-cells-and-related-mechanism
#16
Min Zhang, Yunjian Wang, Qiong Li, Qingjun Li, Nanmu Yang, Guohua You, Li Wang
Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 μmol/L)...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28712397/-stem-cell-factor-enhances-invasive-ability-of-bxpc-3-cells-via-hypoxia-inducible-factor-1%C3%AE-hif-1%C3%AE
#17
Min Zhang, Kang Guo, Qiong Li, Yunjian Wang, Ling Zhang, Tao He, Baishun Wan, Xiaoqian Wang
Objective To investigate the effect of stem cell factor (SCF)/c-KIT system on the invasion of BxPC-3 pancreatic cancer cells and the role of hypoxia-inducible factor 1 alpha (HIF-1α) in this effect. Methods BxPC-3 cells were cultured in normoxia and hypoxia. The cells cultured in normoxia were treated with SCF. Real-time quantitative PCR and Western blotting were used to investigate the expressions of HIF-1α mRNA and protein, respectively. Small interference RNA of HIF-1α (siHIF-1α) was designed and synthesized, and then transfected into BxPC-3 cells...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28710377/antiangiogenic-activity-of-phthalides-enriched-angelica-sinensis-extract-by-suppressing-wsb-1-pvhl-hif-1%C3%AE-vegf-signaling-in-bladder-cancer
#18
Meng-Chuan Chen, Wen-Lin Hsu, Wen-Liang Chang, Tz-Chong Chou
The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709643/hypoxia-induced-suppression-of-c-myc-by-hif-2%C3%AE-in-human-pulmonary-endothelial-cells-attenuates-tfam-expression
#19
Ali J Zarrabi, Derrick Kao, Dustin T Nguyen, Joseph Loscalzo, Diane E Handy
The adaptive response to hypoxia is mediated in large part by stabilization of the hypoxia-inducible factors, HIF-1α and HIF-2α. A hallmark of this response is the metabolic shift to decreased oxidative phosphorylation and increased glycolysis. We hypothesized that hypoxic responses would include a suppression of mitochondrial gene expression. We determined the effects of hypoxia on TFAM, a key mitochondrial transcription factor, in normal pulmonary artery endothelial cells. Hypoxia decreased gene expression of TFAM and that of its upstream regulator, the transcriptional co-activator PGC1β...
July 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28709637/tubulointerstitial-fibrosis-can-sensitize-the-kidney-to-subsequent-glomerular-injury
#20
Beom Jin Lim, Jae Won Yang, Jun Zou, Jianyong Zhong, Taiji Matsusaka, Ira Pastan, Ming-Zhi Zhang, Raymond C Harris, Hai-Chun Yang, Agnes B Fogo
Chronic glomerular injury is associated with eventual development of tubulointerstitial fibrosis. Here we aimed to assess whether, and how, mild chronic tubulointerstitial injury affects glomeruli. For this, we generated mice expressing different toxin receptors, one on their proximal tubular epithelial cells (diphtheria toxin receptor [DTR]) and the other only on podocytes (human CD25 [IL-2R] driven by the nephrin promoter [Nep25]), allowing serial induction of tubule-specific and glomerular (podocyte)-specific injury, respectively...
July 12, 2017: Kidney International
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