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Hypoxia inducible factor

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https://www.readbyqxmd.com/read/28231563/hypoxia-pathway-mutations-in-pheochromocytomas-and-paragangliomas
#1
Diana Amorim-Pires, Joana Peixoto, Jorge Lima
Pheochromocytomas (PCC) and sympathetic paragangliomas (PGL) are rare neuroendocrine tumors, which derive from chromaffin cells occurring in the adrenal medulla and extra-adrenal sympathetic paraganglia. PCC and PGL are often benign, catecholamine-producing tumors, responsible for a myriad of symptoms that may be potentially hazardous to the patient. In contrast, nonsecreting parasympathetic PGL, derived from chief cells, develop mainly in the head and neck region. Although PCC/PGL are more commonly sporadic tumors, germline mutations are present in up to 40% of the patients, ranking these tumors among those with the highest degree of heritability...
February 24, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28230861/ripk3-interactions-with-mlkl-and-camkii-mediate-oligodendrocytes-death-in-the-developing-brain
#2
Yi Qu, Jun Tang, Huiqing Wang, Shiping Li, Fengyan Zhao, Li Zhang, Q Richard Lu, Dezhi Mu
Oligodendrocyte progenitor cells (OPCs) death is a key contributor to cerebral white matter injury (WMI) in the developing brain. A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD/zVAD) in vitro...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230075/oxygen-impairs-oligodendroglial-development-via-oxidative-stress-and-reduced-expression-of-hif-1%C3%AE
#3
Christina Brill, Till Scheuer, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
The premature increase of oxygen tension may contribute to oligodendroglial precursor cell (OPC) damage in preterm infants. Fetal OPCs are exposed to low oxygen tissue tensions not matched when cells are cultured in room air. Maturation (A2B5, O4, O1, MBP, CNP, arborization), oxidative stress (nitrotyrosine Western blot, NRF2 and SOD2 expression), apoptosis (TUNEL), proliferation (Ki67), and expression of transcription factors regulated by Hypoxia-Inducible-Factor-1-alpha (Hif-1α) expressed in OPCs (Olig1, Olig2, Sox9, Sox10) were assessed in rat OPCs and OLN93 cells cultured at 5% O2 and 21% O2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229048/anaplasma-phagocytophilum-infection-subverts-carbohydrate-metabolic-pathways-in-the-tick-vector-ixodes-scapularis
#4
Alejandro Cabezas-Cruz, Pilar Alberdi, James J Valdés, Margarita Villar, José de la Fuente
The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28228417/oxygen-sensitive-regulation-and-neuroprotective-effects-of-growth-hormone-dependent-growth-factors-during-early-postnatal-development
#5
Susan Jung, Gudrun Boie, Helmuth-Guenther Doerr, Regina Trollmann
Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIF) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyse effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (ELISA) and mRNA levels (quantitative RT PCR) of growth factors in plasma and brain between normoxic and hypoxic mice (8% O2, 6 h; postnatal day 7, P7) at P14...
February 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28228260/chemotherapy-induced-ca-2-release-stimulates-breast-cancer-stem-cell-enrichment
#6
Haiquan Lu, Ivan Chen, Larissa A Shimoda, Youngrok Park, Chuanzhao Zhang, Linh Tran, Huimin Zhang, Gregg L Semenza
Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor 1 (HIF-1) and HIF-2. Knockdown of GSTO1 expression abrogates carboplatin-induced BCSC enrichment, decreases tumor initiation and metastatic capacity, and delays tumor recurrence after chemotherapy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225008/anticancer-osmium-complex-inhibitors-of-the-hif-1%C3%AE-and-p300-protein-protein-interaction
#7
Chao Yang, Wanhe Wang, Guo-Dong Li, Hai-Jing Zhong, Zhen-Zhen Dong, Chun-Yuen Wong, Daniel W J Kwong, Dik-Lung Ma, Chung-Hang Leung
The hypoxia inducible factor (HIF) pathway has been considered to be an attractive anti-cancer target. One strategy to inhibit HIF activity is through the disruption of the HIF-1α-p300 protein-protein interaction. We report herein the identification of an osmium(II) complex as the first metal-based inhibitor of the HIF-1α-p300 interaction. We evaluated the effect of complex 1 on HIF-1α signaling pathway in vitro and in cellulo by using the dual luciferase reporter assay, co-immunoprecipitation assay, and immunoblot assay...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223135/cell-physiology-regulation-by-hypoxia-inducible-factor-1-targeting-oxygen-related-nanomachineries-of-hypoxic-cells
#8
REVIEW
Morteza Eskandani, Somayeh Vandghanooni, Jaleh Barar, Hossein Nazemiyeh, Yadollah Omidi
Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions...
February 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28222071/combination-of-the-histone-deacetylase-inhibitor-vorinostat-with-bevacizumab-in-patients-with-clear-cell-renal-cell-carcinoma-a-multicentre-single-arm-phase-i-ii-clinical-trial
#9
Roberto Pili, Glenn Liu, Sreenivasulu Chintala, Hendrick Verheul, Shabnam Rehman, Kristopher Attwood, Martin A Lodge, Richard Wahl, James I Martin, Kiersten Marie Miles, Silvia Paesante, Remi Adelaiye, Alejandro Godoy, Serina King, James Zwiebel, Michael A Carducci
BACKGROUND: Class II histone deacetylase (HDAC) inhibitors induce hypoxia-inducible factor-1 and -2α degradation and have antitumour effects in combination with vascular endothelial growth factor (VEGF) inhibitors. In this study, we tested the safety and efficacy of the HDAC inhibitor vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients previously treated with different drugs including sunitinib, sorafenib, axitinib, interleukin-2, interferon, and temsirolimus...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#10
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28221004/systems-biology-of-oxygen-homeostasis
#11
REVIEW
Debangshu Samanta, Nanduri R Prabhakar, Gregg L Semenza
Metazoan species maintain oxygen homeostasis through the activity of hypoxia-inducible factors, which are transcriptional activators that regulate the expression of hundreds of genes to match O2 supply and demand. Here, we review the involvement of hypoxia-inducible factors in the molecular physiology and pathophysiology of cellular O2 sensing, O2 delivery, O2 utilization, and systemic O2 sensing. For further resources related to this article, please visit the WIREs website.
February 21, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28220896/mitochondrial-dysregulation-secondary-to-endoplasmic-reticulum-stress-in-autosomal-dominant-tubulointerstitial-kidney-disease-umod-adtkd-umod
#12
Elisabeth Kemter, Thomas Fröhlich, Georg J Arnold, Eckhard Wolf, Rüdiger Wanke
'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220024/molecular-subtypes-improve-prognostic-value-of-international-metastatic-renal-cell-carcinoma-database-consortium-prognostic-model
#13
Guillermo de Velasco, Aedín C Culhane, André P Fay, A Ari Hakimi, Martin H Voss, Nizar M Tannir, Pheroze Tamboli, Leonard J Appleman, Joaquim Bellmunt, W Kimryn Rathmell, Laurence Albiges, James J Hsieh, Daniel Y C Heng, Sabina Signoretti, Toni K Choueiri
INTRODUCTION: Gene-expression signatures for prognosis have been reported in localized renal cell carcinoma (RCC). The aim of this study was to test the predictive power of two different signatures, ClearCode34, a 34-gene signature model [Eur Urol 2014;66:77-84], and an 8-gene signature model [Eur Urol 2015;67:17-20], in the setting of systemic therapy for metastatic disease. MATERIALS AND METHODS: Metastatic RCC (mRCC) patients from five institutions who were part of TCGA were identified and clinical data were retrieved...
February 20, 2017: Oncologist
https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#14
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219680/the-regulation-of-transcriptional-repression-in-hypoxia
#15
Miguel A S Cavadas, Alex Cheong, Cormac T Taylor
A sufficient supply molecular oxygen is essential for the maintenance of physiologic metabolism and bioenergetic homeostasis for most metazoans. For this reason, mechanisms have evolved for eukaryotic cells to adapt to conditions where oxygen demand exceeds supply (hypoxia). These mechanisms rely on the modification of pre-existing proteins, translational arrest and transcriptional changes. The hypoxia inducible factor (HIF; a master regulator of gene induction in response to hypoxia) is responsible for the majority of induced gene expression in hypoxia...
February 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28218996/hypoxia-stimulated-membrane-trafficking-requires-t-plastin
#16
Marieke Wottawa, Stephanie Naas, Johannes Böttger, Gijsbert J van Belle, Wiebke Möbius, Natalia H Revelo, Doris Heidenreich, Melanie von Ahlen, Anke Zieseniss, Katharina Kröhnert, Susanne Lutz, Christof Lenz, Henning Urlaub, Silvio O Rizzoli, Dörthe M Katschinski
Traffic between the plasma membrane and the endomembrane compartments is an essential feature of eukaryotic cells. The secretory pathway sends cargoes from biosynthetic compartments to the plasma membrane. This is counterbalanced by a retrograde endocytotic route and is essential for cell homeostasis. Cells need to adapt rapidly to environmental challenges like the reduction of pO2 which, however, has not been analyzed in relation to membrane trafficking in detail. Therefore we determined changes in the plasma membrane trafficking in normoxia, hypoxia, and after reoxygenation METHODS: Membrane trafficking was analyzed by using the bulk membrane endocytosis marker FM 1-43, the newly developed membrane probe mCLING, wheat germ agglutinin as well as fluorescently labeled choleratoxin subunit B...
February 20, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28217462/the-therapeutic-potential-of-hif-2-antagonism-in-renal-cell-carcinoma
#17
COMMENT
Olivier Cuvillier
Hypoxia, the insufficient delivery of oxygen for the demand of a tissue, contributes to the development of an aggressive phenotype, resistance to radiation therapy and chemotherapy, and is predictive of a poor outcome in numerous tumor types. Adaptation to hypoxia is mediated by hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, which regulate genes promoting angiogenesis, increased tumor growth or metastasis. In kidney cancer, HIF-2α is believed to be the most important driver for development and progression of clear cell renal cell carcinoma (ccRCC), highlighting the therapeutic potential of HIF-2 antagonists in this disease...
February 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28216876/wheatgrass-extract-ameliorates-hypoxia-induced-mucin-gene-expression-in-a549-cells
#18
Ju Hwan Sim, Moon-Hee Choi, Hyun-Jae Shin, Ji-Eun Lee
BACKGROUND: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. OBJECTIVE: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. MATERIALS AND METHODS: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216300/boronic-acid-tethered-amphiphilic-hyaluronic-acid-derivative-based-nanoassemblies-for-tumor-targeting-and-penetration
#19
Jae Young Jeong, Eun-Hye Hong, Song Yi Lee, Jae-Young Lee, Jae-Hyoung Song, Seung-Hak Ko, Jae-Seong Shim, Sunghwa Choe, Dae-Duk Kim, Hyun-Jeong Ko, Hyun-Jong Cho
(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and > 90% drug encapsulation efficiency were fabricated...
February 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28216142/astrocytic-calcium-waves-signal-brain-injury-to-neural-stem-and%C3%A2-progenitor%C3%A2-cells
#20
Anna Kraft, Eduardo Rosales Jubal, Ruth von Laer, Claudia Döring, Adriana Rocha, Moyo Grebbin, Martin Zenke, Helmut Kettenmann, Albrecht Stroh, Stefan Momma
Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia...
February 3, 2017: Stem Cell Reports
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