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HIF-1a and metabolism

Martin Böttcher, Kathrin Renner, Raffaela Berger, Kristin Mentz, Simone Thomas, Zugey Elizabeth Cardenas-Conejo, Katja Dettmer, Peter J Oefner, Andreas Mackensen, Marina Kreutz, Dimitrios Mougiakakos
D-2-hydroxyglutarate (D-2HG) is released by various types of malignant cells including acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. D-2HG acting as an oncometabolite promotes proliferation, anoikis, and differentiation block of hematopoietic cells in an autocrine fashion. However, prognostic impact of IDH mutations and high D-2HG levels remains controversial and might depend on the overall mutational context. An increasing number of studies focus on the permissive environment created by AML blasts to promote immune evasion...
2018: Oncoimmunology
Jie Wei, Jun Wu, Wen Xu, Hong Nie, Ruiqing Zhou, Rui Wang, Yang Liu, Guoyao Tang, Jianyong Wu
Our previous study demonstrated a progressive glycolytic perturbation during the course of DMBA-induced hamster oral carcinogenesis, which was attenuated by salvianolic acid B (Sal-B) treatment along with decreased incidences of oral squamous cell carcinoma (OSCC) formation. It was proposed that metabolic modulation should be an additional mode of action attributable to Sal-B's anti-carcinogenic activity. However, the molecular mechanisms underlying Sal-B-induced metabolic modulation function remained elusive...
May 22, 2018: Cell Death & Disease
Yingyu Zhou, Cuilin Cheng, Denis Baranenko, Jiaping Wang, Yongzhi Li, Weihong Lu
The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse...
January 15, 2018: International Journal of Molecular Sciences
Weinan Du, Luchang Zhang, Adina Brett-Morris, Brittany Aguila, Janos Kerner, Charles L Hoppel, Michelle Puchowicz, Dolors Serra, Laura Herrero, Brian I Rini, Steven Campbell, Scott M Welford
Clear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor stabilizing the hypoxia-inducible factors (HIFs) are the most prevalent molecular features of clear cell tumors. The significance of lipid deposition remains undefined. We describe the mechanism of lipid deposition in ccRCC by identifying the rate-limiting component of mitochondrial fatty acid transport, carnitine palmitoyltransferase 1A (CPT1A), as a direct HIF target gene...
November 24, 2017: Nature Communications
Aurélia Nguyen, François Marie Moussallieh, Alan Mackay, A Ercument Cicek, Andres Coca, Marie Pierre Chenard, Noelle Weingertner, Benoit Lhermitte, Eric Letouzé, Eric Guérin, Erwan Pencreach, Sarah Jannier, Dominique Guenot, Izzie Jacques Namer, Chris Jones, Natacha Entz-Werlé
Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions...
March 23, 2017: Oncotarget
Young-Ju Jeong, Jae-Won Jung, Yoon-Young Cho, Sung-Hwan Park, Hoon-Kyu Oh, Sungmin Kang
BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed...
2017: Nuclear Medicine Review. Central & Eastern Europe
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 centres (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen-activated B cells proliferate, express high-affinity antibodies, promote antibody class switching, and yield B cell memory. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class, both cell-autonomous and extrinsic metabolic programming have emerged as modulators of T-cell-mediated immunity. Here we show in mice that GC light zones are hypoxic, and that low oxygen tension () alters B cell physiology and function...
September 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...
October 9, 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
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