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Hypoxia inducible factor

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https://www.readbyqxmd.com/read/28531964/non-electron-transfer-chain-mitochondrial-defects-differently-regulate-hif-1%C3%AE-degradation-and-transcription
#1
Antonina N Shvetsova, Daniela Mennerich, Juha M Kerätär, J Kalervo Hiltunen, Thomas Kietzmann
Mitochondria are the main consumers of molecular O2 in a cell as well as an abundant source of reactive oxygen species (ROS). Both, molecular oxygen and ROS are powerful regulators of the hypoxia-inducible factor-1α-subunit (HIF-α). While a number of mechanisms in the oxygen-dependent HIF-α regulation are quite well known, the view with respect to mitochondria is less clear. Several approaches using pharmacological or genetic tools targeting the mitochondrial electron transport chain (ETC) indicated that ROS, mainly formed at the Rieske cluster of complex III of the ETC, are drivers of HIF-1α activation...
May 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/28529605/mutual-regulation-of-mir-199a-5p-and-hif-1%C3%AE-modulates-the-warburg-effect-in-hepatocellular-carcinoma
#2
Binkui Li, Liru He, Dinglan Zuo, Wei He, Yongjin Wang, Yuanping Zhang, Wenwu Liu, Yunfei Yuan
The Warburg effect is one of the major metabolic changes of cancer cells, which characterized by high level of glycolysis even in the presence of oxygen. However, the role of microRNAs (miRNAs) in regulating the glycolytic switch in cancer cells has not been well explored. In this study, we demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in hepatocellular carcinoma (HCC). MiR-199a-5p directly targets the 3'-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529559/fbp1-expression-is-associated-with-basal-like-breast-carcinoma
#3
Lei Shi, Chunbo Zhao, Haihong Pu, Qingyuan Zhang
The present study aimed to investigate the value of liver fructose 1,6-bisphophatase (FBP1) and hypoxia-inducible factor-1α (HIF-1α) in the molecular subtyping of breast carcinoma. Tissue obtained from 60 surgical specimens from patients with breast carcinoma underwent immunohistochemical staining for cytokeratin 5/6, HIF-1α and FBP1. The variation in the expression levels of these markers and clinicopathological factors were compared between molecular subtypes. In addition, disease-free survival was compared between basal-like and luminal breast carcinoma, according to differing expression levels of HIF-1α and FBP1...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529459/cold-inducible-rna-binding-protein-is-involved-in-chronic-hypoxia-induced-neuron-apoptosis-by-down-regulating-hif-1%C3%AE-expression-and-regulated-by-microrna-23a
#4
Xiaoming Chen, Xinqin Liu, Bin Li, Qian Zhang, Jiye Wang, Wenbin Zhang, Wenjing Luo, Jingyuan Chen
Background: Neuron apoptosis mediated by hypoxia inducible factor 1α (HIF-1α) in hippocampus is one of the most important factors accounting for the chronic hypobaric hypoxia induced cognitive impairment. As a neuroprotective molecule that is up-regulated in response to various environmental stress, CIRBP was reported to crosstalk with HIF-1α under cellular stress. However, its function under chronic hypobaric hypoxia remains unknown. Objective: In this study, we tried to identify the role of CIRBP in HIF-1α mediated neuron apoptosis under chronic hypobaric hypoxia and find a possible method to maintain its potential neuroprotective in long-term high altitude environmental exposure...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28528514/tissue-metabolism-and-the-inflammatory-bowel-diseases
#5
REVIEW
Jordi M Lanis, Daniel J Kao, Erica E Alexeev, Sean P Colgan
The intestinal mucosa provides a selective barrier between the anaerobic lumen and a highly metabolic lamina propria. A number of recent studies indicate that acute inflammation of the mucosa can result in tissue hypoxia and associated shifts in tissue metabolism. The activation of hypoxia-inducible factor (HIF) under these conditions has been demonstrated to function as an endogenous molecular cue to promote resolution of inflammation, particularly through the orchestration of barrier repair toward homeostasis...
May 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28527810/hif-1%C3%AE-stabilizing-agent-fg-4997-rescues-human-cd34-cell-mobilization-in-response-to-g-csf-in-immuno-deficient-mice
#6
Bianca Nowlan, Katarzyna Futrega, Marion E Brunck, Gail Walkinshaw, Lee E Flippin, Michael R Doran, Jean-Pierre Levesque
Granulocyte colony-stimulating factor (G-CSF) is routinely used in the clinic to mobilize hematopoietic stem progenitor cells (HSPC) into the patient's blood for collection and subsequent transplantation. However a significant proportion of patients who have previously received chemotherapy or radiotherapy and requiring autologous HSPC transplantation, cannot mobilize the minimal threshold of mobilized HSPC to achieve rapid and successful hematopoietic reconstitution. Although several alternatives to the G-CSF regime have been tested, few are in use in the clinic...
May 17, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28527294/activation-of-hypoxia-signaling-in-stromal-progenitors-impairs-kidney-development
#7
Katharina Gerl, Dominik Steppan, Michaela Fuchs, Charlotte Wagner, Carsten Willam, Armin Kurtz, Birgül Kurt
Intrauterine hypoxia is a reason for impaired kidney development. The cellular and molecular pathways along which hypoxia exerts effects on nephrogenesis are not well understood. They are likely triggered by hypoxia-inducible transcription factors (HIFs), and their effects appear to be dependent on the cell compartment contributing to kidney formation. In this study, we investigated the effects of HIF activation in the developing renal stroma, which also essentially modulates nephron development from the metanephric mesenchyme...
May 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28526501/hypoxia-modulates-cell-migration-and-proliferation-in-placenta-derived-mesenchymal-stem-cells
#8
Li Li, Prashant Kumar Jaiswal, Georges Makhoul, Rishi Jurakhan, Kaviyanka Selvasandran, Khalid Ridwan, Renzo Cecere
OBJECTIVES: For more than a decade, stem cells isolated from different tissues have been evaluated in cell therapy. Among them, the human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were investigated extensively in the treatment of myocardial infarction. Recently, the human placenta-derived mesenchymal stem cells (hPD-MSCs), which are readily available from a biological waste, appear to be a viable alternative to hBM-MSCs. METHODS: C-X-C chemokine receptor type 4 (CXCR4) gene expression and localization were detected and validated in hPD-MSCs and hBM-MSCs via polymerase chain reaction and immunofluorescence...
April 13, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28526405/hypoxia-inducible-factor-l%C3%AE-mediates-aggrecan-and-collagen-%C3%AE-expression-via-notch1-signaling-in-nucleus-pulposus-cells-during-intervertebral-disc-degeneration
#9
Zhuochao Liu, Changwei Li, Xiangchao Meng, Yunting Bai, Jin Qi, Jun Wang, Qi Zhou, Weibin Zhang, Xingkai Zhang
Although hypoxia-inducible factor-lα (HIF-lα) has been reported to have an important role in the metabolism and synthesis of the extracellular matrix (ECM) of nucleus pulposus cells (NPCs), the underlying mechanism has not been fully clarified. Here, we show for the first time that NOTCH1 expression is decreased in NPs isolated from degenerated human intervertebral discs (IVDs), as well as in the NPs of NP-specific HIF-1α(-/-) mice. Our study reveals that overexpression of HIF-1α leads to increased expression of NOTCH1, the NOTCH1 ligand JAGGED1, and its target gene hairy and enhancer of split-1 (HES1), while also upregulating collagen Π and aggrecan expression in human NPCs...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526370/synthesis-and-biological-evaluation-of-kresoxim-methyl-analogues-as-novel-inhibitors-of-hypoxia-inducible-factor-hif-1-accumulation-in-cancer-cells
#10
Sanghyuck Lee, Oh Seok Kwon, Chang-Soo Lee, Misun Won, Hyun Seung Ban, Choon Sup Ra
We designed and synthesized strobilurin analogues as hypoxia-inducible factor (HIF) inhibitors based on the molecular structure of kresoxim-methyl. Biological evaluation in human colorectal cancer HCT116 cells showed that most of the synthesized kresoxim-methyl analogues possessed moderate to potent inhibitory activity against hypoxia-induced HIF-1 transcriptional activation. Three candidates, compounds 11b, 11c, and 11d were identified as potent inhibitors against HIF-1 activation with IC50 values of 0.60-0...
May 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28526262/hypoxic-pathobiology-of-breast-cancer-metastasis
#11
REVIEW
Luana Schito, Sergio Rey
Dissemination of breast cancer cells (BCCs) to distant sites (metastasis) is the ultimate cause of mortality in patient with breast cancer. Hypoxia (low O2) is a microenvironmental hallmark of most solid cancers arising as a mismatch between cellular O2 consumption and supply. Hypoxic selection of BCCs triggers molecular and cellular adaptations dependent upon hypoxia-inducible factors (HIFs), a family of evolutionarily conserved transcriptional activators that coordinate the expression of numerous genes controlling each step of the metastatic process...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28525945/the-protective-effect-of-luteolin-on-myocardial-ischemia-reperfusion-i-r-injury-through-tlr4-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-pathway
#12
Xu Zhang, Qianming Du, Yan Yang, Jianing Wang, Shuai Dou, Chao Liu, Junguo Duan
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM)...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28525553/evaluation-of-conventional-and-frozen-elephant-trunk-techniques-on-spinal-cord-blood-flow-in-an-animal-model%C3%A2
#13
Sergey Leontyev, Maja-Theresa Dieterlen, Michelle Halling, Franziska Schlegel, Alexandro Hoyer, Susann Ossmann, Kerstin Klaeske, Christian D Etz, Friedrich W Mohr
OBJECTIVES: The treatment of patients with extensive thoracic aortic disease involving the arch and descending aorta is often performed using the frozen elephant trunk technique (FET). Spinal cord blood flow (SCBF) in cervical, thoracic and lumbar sections prior, during and after aortic arch surgery were compared in conventional elephant trunk (cET) and FET technique in a pig model. METHODS: German Landrace pigs (75-85 kg) underwent aortic arch surgery using the FET ( n  = 8) or cET ( n  = 8) techniques...
May 18, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28525507/subcellular-energetics-and-metabolism-a-cross-species-framework
#14
Robert H Thiele
Although it is generally believed that oxidative phosphorylation and adequate oxygenation are essential for life, human development occurs in a profoundly hypoxic environment and "normal" levels of oxygen during embryogenesis are even harmful. The ability of embryos not only to survive but also to thrive in such an environment is made possible by adaptations related to metabolic pathways. Similarly, cancerous cells are able not only to survive but also to grow and spread in environments that would typically be fatal for healthy adult cells...
June 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28524833/promoting-vasa-vasorum-neovascularization-of-vein-grafts-extenuates-hypoxia-of-the-wall-and-its-subsequent-influence-on-intimal-hyperplasia
#15
Rong-Jiang Zou, Zheng-Hua Wang, Chen-Xi Wang, Song Xue
BACKGROUND: The autologous saphenous vein is the most common conduit for coronary artery bypass grafting, but the vein graft disease will occur. This study used Matrigel basement membrane matrix with many different growth factors to promote vasa vasorum neovascularization and extenuate the hypoxia to improve remodeling. METHODS: This study observed the hypoxia and thickness of the vein grafts at different times. Normal veins and vein grafts with 15 min of ischemia one day postoperatively were harvested in the neck of rabbits...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28523034/effects-of-sirna-mediated-hif-1%C3%AE-gene-silencing-on-angiogenesis-in-osteosarcoma
#16
Xu-Dong Zhang, Qiang Wu, Shu-Hua Yang
OBJECTIVE: To explore angiogenesis in osteosarcoma under the condition of hypoxia-inducible factor (HIF)-1α gene silenced by small interference RNA (siRNA). METHODS: The SaOS-2 osteosarcoma cells, transfected with the recombinant plasmid pSilencer2.1-HIF-1α or pSilencer2.1-SCR, were classified as HIF-1α/siRNA group or SCR/siRNA group, respectively. In which, vascular endothelial growth factor (VEGF) immunohistochemistry were performed. HIF-1α and VEGF protein contents were detected by western blot...
March 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28522758/regulation-of-erythropoiesis-after-normoxic-return-from-chronic-sustained-and-intermittent-hypoxia
#17
Jihyun Song, Krishna Sundar, Radhika Gangaraju, Josef T Prchal
Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF) which regulate erythropoietin (EPO) transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia (CSH) by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species (ROS) in reticulocytes mediated by down-regulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#18
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522568/peroxisome-proliferator-activated-receptor-gamma-enhances-human-pulmonary-artery-smooth-muscle-cell-apoptosis-through-microrna-21-and-programmed-cell-death-4
#19
David Emerson Green, Tamara C Murphy, Bum-Yong Kang, Brahmchetna Bedi, Zhihong Yuan, Ruxana T Sadikot, C Michael Hart
Pulmonary hypertension (PH) is a progressive disorder whose cellular pathogenesis involves enhanced smooth muscle cell (SMC) proliferation and resistance to apoptosis signals. Existing evidence demonstrates that the tumor suppressor, programmed cell death 4 (PDCD4) affects patterns of cell growth and repair responses in the systemic vasculature following experimental injury. In the current study, the regulation PDCD4 and its functional effects on growth and apoptosis susceptibility in pulmonary artery smooth muscle cells was explored...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28521842/clinical-and-prognostic-significance-of-hif-1%C3%AE-overexpression-in-oral-squamous-cell-carcinoma-a-meta-analysis
#20
Jianhua Zhou, Shengyun Huang, Lili Wang, Xiao Yuan, Quanjiang Dong, Dongsheng Zhang, Xuxia Wang
BACKGROUND: Recent studies have indicated an association between hypoxia inducible factor-1 alpha (HIF-1α) expression and poor prognosis in patients with oral squamous cell carcinoma (OSCC); however, definitive evidence of this association is yet to be obtained. We performed a meta-analysis to evaluate the association of HIF-1α expression with clinicopathological characteristics and overall survival (OS) of patients with OSCC. METHODS: A literature search for relevant studies published in English language as of February 05, 2016, was performed on PubMed, Web of Science, and EMBASE databases...
May 18, 2017: World Journal of Surgical Oncology
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