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HIF-1a and metabolism

Sung Hoon Cho, Ariel L Raybuck, Kristy Stengel, Mei Wei, Thomas C Beck, Emmanuel Volanakis, James W Thomas, Scott Hiebert, Volker H Haase, Mark R Boothby
Germinal centers (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen (Ag)-activated B lymphocytes proliferate, are selected for high affinity antibody (Ab), promote Ab class switching, and yield B cell memory1,2. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class 3,4, both cell-autonomous5 and extrinsic6,7 metabolic programming have emerged as modulators of T cell-mediated immunity8. We now show that GC light zones are hypoxic and low oxygen (pO2) alters B cell physiology and function...
August 8, 2016: Nature
Yunseon Jang, Jeongsu Han, Soo Jeong Kim, Jungim Kim, Min Joung Lee, Soyeon Jeong, Min Jeong Ryu, Kang-Sik Seo, Song-Yi Choi, Minho Shong, Kyu Lim, Jun Young Heo, Gi Ryang Kweon
Renal cell carcinoma (RCC) progression resulting from the uncontrolled migration and enhanced angiogenesis is an obstacle to effective therapeutic intervention. Tumor metabolism has distinctive feature called Warburg effect, which enhances the aerobic glycolysis rapidly supplying the energy for migration of tumor. To manipulate this metabolic change characteristic of aggressive tumors, we utilized the citrus extract, auraptene, known as a mitochondrial inhibitor, testing its anticancer effects against the RCC4 cell line...
November 10, 2015: Oncotarget
Ying Wang, Liandong Yang, Kun Zhou, Yanping Zhang, Zhaobin Song, Shunping He
Triplophysa fishes are the primary component of the fish fauna on the Tibetan Plateau and are well adapted to the high-altitude environment. Despite the importance of Triplophysa fishes on the plateau, the genetic mechanisms of the adaptations of these fishes to this high-altitude environment remain poorly understood. In this study, we generated the transcriptome sequences for three Triplophysa fishes, that is, Triplophysa siluroides, Triplophysa scleroptera, and Triplophysa dalaica, and used these and the previously available transcriptome and genome sequences from fishes living at low altitudes to identify potential genetic mechanisms for the high-altitude adaptations in Triplophysa fishes...
November 2015: Genome Biology and Evolution
Luis J Garcia-Morales, Ning-Yuan Chen, Tingting Weng, Fayong Luo, Jonathan Davies, Kemly Philip, Kelly A Volcik, Ernestina Melicoff, Javier Amione-Guerra, Raquel R Bunge, Brian A Bruckner, Matthias Loebe, Holger K Eltzschig, Lavannya M Pandit, Michael R Blackburn, Harry Karmouty-Quintana
Group III pulmonary hypertension (PH) is a highly prevalent and deadly lung disorder with limited treatment options other than transplantation. Group III PH affects patients with ongoing chronic lung injury, such as idiopathic pulmonary fibrosis (IPF). Between 30 and 40% of patients with IPF are diagnosed with PH. The diagnosis of PH has devastating consequences to these patients, leading to increased morbidity and mortality, yet the molecular mechanisms involved in the development of PH in patients with chronic lung disease remain elusive...
April 2016: American Journal of Respiratory Cell and Molecular Biology
Joanna Kopecka, Stefania Porto, Sara Lusa, Elena Gazzano, Giuseppina Salzano, Antonio Giordano, Vincenzo Desiderio, Dario Ghigo, Michele Caraglia, Giuseppe De Rosa, Chiara Riganti
The overexpression of ATP binding cassette (ABC) transporters makes tumor cells simultaneously resistant to several cytotoxic drugs. Impairing the energy metabolism of multidrug resistant (MDR) cells is a promising chemosensitizing strategy, but many metabolic modifiers are too toxic in vivo. We previously observed that the aminobisphosphonate zoledronic acid inhibits the activity of hypoxia inducible factor-1a (HIF-1a), a master regulator of cancer cell metabolism. Free zoledronic acid, however, reaches low intratumor concentration...
October 13, 2015: Oncotarget
Farid Ahmed, Stefan Plantman, Ibolja Cernak, Denes V Agoston
Time-dependent changes in blood-based protein biomarkers can help identify the -pathological processes in blast-induced traumatic brain injury (bTBI), assess injury severity, and monitor disease progression. We obtained blood from control and injured mice (exposed to a single, low-intensity blast) at 2-h, 1-day, 1-week, and 1-month post-injury. We then determined the serum levels of biomarkers related to metabolism (4-HNE, HIF-1α, ceruloplasmin), vascular function (AQP1, AQP4, VEGF, vWF, Flk-1), inflammation (OPN, CINC1, fibrinogen, MIP-1a, OX-44, p38, MMP-8, MCP-1 CCR5, CRP, galectin-1), cell adhesion and the extracellular matrix (integrin α6, TIMP1, TIMP4, Ncad, connexin-43), and axonal (NF-H, Tau), neuronal (NSE, CK-BB) and glial damage (GFAP, S100β, MBP) at various post-injury time points...
2015: Frontiers in Neurology
W J Piotrowski, J Kiszałkiewicz, D Pastuszak-Lewandoska, P Górski, A Antczak, M Migdalska-Sęk, W Górski, K H Czarnecka, D Domańska, E Nawrot, E Brzeziańska-Lasota
Angiogenesis/angiostasis regulated by hypoxia inducible factor-1A (HIF-1A)/vascular endothelial growth factor (VEGF)/inhibitor of growth protein 4 (ING-4) axis may be crucial for the course and outcome of sarcoidosis. Overexpression of angiogenic factors (activation of VEGF through HIF-1A) may predispose to chronic course and lung fibrosis, whereas immunoangiostasis (related to an overexpression of inhibitory ING-4) may be involved in granuloma formation in early sarcoid inflammation, or sustained or recurrent formation of granulomas...
2015: Advances in Experimental Medicine and Biology
Kurosh Ameri, Arman Jahangiri, Anthony M Rajah, Kathryn V Tormos, Ravi Nagarajan, Melike Pekmezci, Vien Nguyen, Matthew L Wheeler, Michael P Murphy, Timothy A Sanders, Stefanie S Jeffrey, Yerem Yeghiazarians, Paolo F Rinaudo, Joseph F Costello, Manish K Aghi, Emin Maltepe
Hypoxia-inducible gene domain family member 1A (HIGD1A) is a survival factor induced by hypoxia-inducible factor 1 (HIF-1). HIF-1 regulates many responses to oxygen deprivation, but viable cells within hypoxic perinecrotic solid tumor regions frequently lack HIF-1α. HIGD1A is induced in these HIF-deficient extreme environments and interacts with the mitochondrial electron transport chain to repress oxygen consumption, enhance AMPK activity, and lower cellular ROS levels. Importantly, HIGD1A decreases tumor growth but promotes tumor cell survival in vivo...
February 12, 2015: Cell Reports
Leila Kafshdooz, Ali Dastranj Tabrizi, Seyyed Mojtaba Mohaddes, Tayebeh Kafshdooz, Abolfazl Akbarzadeh, Morteza Ghojazadeh, Jalal Gharesouran
BACKGROUND: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor -1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Fei Zhao, Scott W Malm, Alyssa N Hinchman, Hui Li, Connor G Beeks, Walter T Klimecki
Epidemiology studies have established a strong link between lung cancer and arsenic exposure. Currently, the role of disturbed cellular energy metabolism in carcinogenesis is a focus of scientific interest. Hypoxia inducible factor-1 alpha (HIF-1A) is a key regulator of energy metabolism, and it has been found to accumulate during arsenite exposure under oxygen-replete conditions. We modeled arsenic-exposed human pulmonary epithelial cells in vitro with BEAS-2B, a non-malignant lung epithelial cell line. Constant exposure to 1 µM arsenite (As) resulted in the early loss of anchorage-dependent growth, measured by soft agar colony formation, beginning at 6 weeks of exposure...
2014: PloS One
Jenni M Prokkola, Mikko Nikinmaa, Pedro Lubiana, Mirella Kanerva, R J Scott McCairns, Miriam Götting
Pollution with low concentrations of pharmaceuticals, especially when combined with low-oxygen conditions (hypoxia), is a threat to aquatic ecosystems worldwide. The non-steroidal anti-inflammatory drug diclofenac is commonly detected in wastewater effluents, and has potential to accumulate in the bile of fish. Diclofenac has been shown to activate aryl hydrocarbon receptor (AHR), which induces transcription in the metabolic enzyme cytochrome P450 1a (cyp1a). Previously, crosstalk has been shown to occur between AHR and hypoxia inducible factor 1 (HIF-1)...
January 2015: Aquatic Toxicology
Zhongxin Sun, Wei Shen
OBJECTIVE: To determine the effect of intermittent hypoxia on lipid metabolism in liver cells and to explore the possible molecular pathways involved in this process. METHODS: An intermittent hypoxia cell model system was established by incubating the human hepatic cell lines L02 and HepG2 in an atmosphere of 2% O₂, 5% CO₂ and 93% N₂ for 8 hours per day over a period of 1, 2, 3, 4 or 5 days. Cells cultured in normoxia conditions (21% O₂) served as controls...
May 2014: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Patrizia Sanità, Mattia Capulli, Anna Teti, Giuseppe Paradiso Galatioto, Carlo Vicentini, Paola Chiarugi, Mauro Bologna, Adriano Angelucci
BACKGROUND: Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. METHODS: Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts...
2014: BMC Cancer
Johann Gross, Heidi Olze, Birgit Mazurek
Cells respond to injury and hypoxia by changing gene expression. To study how the main compartments of the cochlea, the stria vascularis (SV), the organ of Corti (OC), and the modiolus (MOD), respond to such stress, we analyzed the expression of selected genes using microarray analysis. Organotypic cultures of SV, OC, and MOD from newborn rats were used as an experimental model. In the present study, we compare the expression of a total of 50 genes involved in apoptosis and necrosis, reactive oxygen species (ROS) metabolism, inflammation as well as selected transcription factors (TF) and analyze their role for the different cell death patterns observed in the three regions...
May 2014: Cellular and Molecular Neurobiology
O Danino, N Giladi, S Grossman, B Fischer
The brain is especially sensitive to oxidative stress due to its high rate of oxidative metabolism, relatively low levels of antioxidant enzymes, and high concentrations of Fe/Cu ions. During the neurodegeneration process, the aggregation of proteins Aβ, accompanies oxidative stress. We explored the potential of thiophosphate derivatives to rescue neurons from oxidative stress and Aβ toxicity. We evaluated the neuroprotective effect of ATP-γ-S, ADP-β-S, and GDP-β-S on primary cortical neuronal cells exposed to several insults, including treatment with FeSO4, co-application of H2O2 and FeSO4, and addition of Aβ42...
April 1, 2014: Biochemical Pharmacology
Yoshihiko Kitajima, Kohji Miyazaki
Hypoxia inducible factor-1 (HIF-1) monitors the cellular response to the oxygen levels in solid tumors. Under hypoxia conditions, HIF-1a protein is stabilized and forms a heterodimer with the HIF-1β subunit. The HIF-1 complex activates the transcription of numerous target genes in order to adapt the hypoxic environment in human cancer cells. In gastric cancer patients, HIF-1a activation following extended hypoxia strongly correlates with an aggressive tumor phenotype and a poor prognosis. HIF-1a activation has been also reported to occur via hypoxia-independent mechanisms such as PI3K/AKT/mTOR signaling and ROS production...
2013: Cancers
Tobias Eckle, Kelley Brodsky, Megan Bonney, Thomas Packard, Jun Han, Christoph H Borchers, Thomas J Mariani, Douglas J Kominsky, Michel Mittelbronn, Holger K Eltzschig
BACKGROUND: While acute lung injury (ALI) contributes significantly to critical illness, it resolves spontaneously in many instances. The majority of patients experiencing ALI require mechanical ventilation. Therefore, we hypothesized that mechanical ventilation and concomitant stretch-exposure of pulmonary epithelia could activate endogenous pathways important in lung protection. METHODS AND FINDINGS: To examine transcriptional responses during ALI, we exposed pulmonary epithelia to cyclic mechanical stretch conditions--an in vitro model resembling mechanical ventilation...
September 2013: PLoS Biology
Takao Matsubara, Gene R Diresta, Shigeki Kakunaga, Dasen Li, John H Healey
BACKGROUND/PURPOSE: The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP) have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using three human osteosarcoma (OS) cell lines and a novel in vitro cell culture apparatus. MATERIALS AND METHODS: U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O2, normoxia 20% O2), and hydrostatic gage pressure (0 or 50 mmHg)...
2013: Frontiers in Oncology
Valentina Bravatà, Alessandro Stefano, Francesco P Cammarata, Luigi Minafra, Giorgio Russo, Stefania Nicolosi, Sabina Pulizzi, Cecilia Gelfi, Maria C Gilardi, Cristina Messa
BACKGROUND: Diagnostic imaging plays a relevant role in the care of patients with breast cancer (BC). Positron Emission Tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has been widely proven to be a clinical tool suitable for BC detection and staging in which the glucose analog supplies metabolic information about the tumor. A limited number of studies, sometimes controversial, describe possible associations between FDG uptake and single nucleotide polymorphisms (SNPs). For this reason this field has to be explored and clarified...
2013: Journal of Experimental & Clinical Cancer Research: CR
Yan Li, Divya Padmanabha, Luciana B Gentile, Catherine I Dumur, Robert B Beckstead, Keith D Baker
Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable...
2013: PLoS Genetics
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