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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/28527256/-stat3-activation-by-hypoxia-in-in-vitro-models-of-cervix-cancer-and-endothelial-cells
#8
Óscar Ortega, Alejandro Ondo-Méndez, Ruth Garzón
INTRODUCTION: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. OBJECTIVE: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526934/exogenous-proline-stimulates-type-i-collagen-and-hif-1%C3%AE-expression-and-the-process-is-attenuated-by-glutamine-in-human-skin-fibroblasts
#9
Lukasz Szoka, Ewa Karna, Kornelia Hlebowicz-Sarat, Jacek Karaszewski, Jerzy A Palka
Abundance of proline (Pro) in collagen molecule led us to investigate whether Pro supply affects collagen biosynthesis in human skin fibroblasts. Treatment of the cells with milimolar concentrations (5 and 10 mM) of Pro for 24 and 48 h contributed to increase in α1 subunit of collagen type I (COL1A1) expression in both cells and culture medium. However, the effect was more pronounced in glutamine-free medium. In such condition, Pro induced collagen expression by about twofold in the cells, while in the medium only by about 30% during 24 h incubation, compared to control...
May 19, 2017: Molecular and Cellular Biochemistry
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
#10
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
#11
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
#12
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/28524872/hif-1%C3%AE-regulates-macrophage-endothelial-interactions-during-blood-vessel-development-in-zebrafish
#13
Claudia Gerri, Rubén Marín-Juez, Michele Marass, Alora Marks, Hans-Martin Maischein, Didier Y R Stainier
Macrophages are known to interact with endothelial cells during developmental and pathological angiogenesis but the molecular mechanisms modulating these interactions remain unclear. Here, we show a role for the Hif-1α transcription factor in this cellular communication. We generated hif-1aa;hif-1ab double mutants in zebrafish, hereafter referred to as hif-1α mutants, and find that they exhibit impaired macrophage mobilization from the aorta-gonad-mesonephros (AGM) region as well as angiogenic defects and defective vascular repair...
May 19, 2017: Nature Communications
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
#14
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
#15
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/28522852/kv3-4-is-modulated-by-hif-1%C3%AE-to-protect-sh-sy5y-cells-against-oxidative-stress-induced-neural-cell-death
#16
Min Seok Song, Pan Dong Ryu, So Yeong Lee
The Kv3.4 channel is characterized by fast inactivation and sensitivity to oxidation. However, the physiological role of Kv3.4 as an oxidation-sensitive channel has yet to be investigated. Here, we demonstrate that Kv3.4 plays a pivotal role in oxidative stress-related neural cell damage as an oxidation-sensitive channel and that HIF-1α down-regulates Kv3.4 function, providing neuroprotection. MPP(+) and CoCl2 are reactive oxygen species (ROS)-generating reagents that induce oxidative stress. However, only CoCl2 decreases the expression and function of Kv3...
May 18, 2017: Scientific Reports
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/28522192/overcoming-photodynamic-resistance-and-tumor-targeting-dual-therapy-mediated-by-indocyanine-green-conjugated-gold-nanospheres
#18
Wei Li, Xiaomeng Guo, Fenfen Kong, Hanbo Zhang, Lihua Luo, Qingpo Li, Chunqi Zhu, Jie Yang, Yongzhong Du, Jian You
Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS)...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28521842/clinical-and-prognostic-significance-of-hif-1%C3%AE-overexpression-in-oral-squamous-cell-carcinoma-a-meta-analysis
#19
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
https://www.readbyqxmd.com/read/28521491/hif-1%C3%AE-acts-as-a-molecular-target-for-simvastatin-cytotoxicity-in-b16-f10-melanoma-cells-cultured-under-chemically-induced-hypoxia
#20
Emilia Licarete, Alina Sesarman, Valentin Florian Rauca, Lavinia Luput, Laura Patras, Manuela Banciu
Our previous studies reported that one of the main mechanisms of the antitumor activity of simvastatin (SIM) in B16.F10 murine melanoma cells was associated with strong suppression of the constitutive cell production of the α subunit of the heterodimeric transcription factor hypoxia-inducible factor (HIF)-1. Thus, the present study aimed to broaden this finding under hypoxic conditions induced by incubation of B16.F10 cells with cobalt chloride, when the constitutive production of HIF-1α in these melanoma cells is amplified by inducible expression of this factor...
May 2017: Oncology Letters
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