Update on hypoxia-inducible factors and hydroxylases in oxygen regulatory pathways: from physiology to therapeutics

The “Hypoxia Nantes 2016” organized its second conference dedicated to the field of hypoxia research. This conference focused on “the role of hypoxia under physiological conditions as well as in cancer” and took place in Nantes, France, in October 6–7, 2016. The main objective of this conference was to bring together a large group of scientists from different spheres of hypoxia. Recent advances were presented and discussed around different topics: genomics, physiology, musculoskeletal, stem cells, microenvironment and cancer, and oxidative stress. This review summarizes the major highlights of the meeting.

[1]  Dean P. Jones,et al.  Redox Proteomics of 4T1 Breast Cancer Cell After Treatment with MnTE-2-PyP5+/Ascorbate System , 2016 .

[2]  P. Carmeliet,et al.  Deficiency of the oxygen sensor prolyl hydroxylase 1 attenuates hypercholesterolaemia, atherosclerosis, and hyperglycaemia. , 2016, European heart journal.

[3]  I. Landrieu,et al.  Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases , 2016, Nature Communications.

[4]  P. Ratcliffe,et al.  Capture‐C reveals preformed chromatin interactions between HIF‐binding sites and distant promoters , 2016, EMBO reports.

[5]  H. Matsunami,et al.  Single cell transcriptome analysis of mouse carotid body glomus cells , 2016, The Journal of physiology.

[6]  Crispin J. Miller,et al.  Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response , 2016, npj Genomic Medicine.

[7]  H. Gelderblom,et al.  Molecular oncogenesis of chondrosarcoma: impact for targeted treatment , 2016, Current opinion in oncology.

[8]  Yue Zhou,et al.  Global profiling of the gene expression and alternative splicing events during hypoxia-regulated chondrogenic differentiation in human cartilage endplate-derived stem cells. , 2016, Genomics.

[9]  P. Fasanaro,et al.  Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing , 2016, Scientific Reports.

[10]  Jiannis Ragoussis,et al.  Benchmarking of the Oxford Nanopore MinION sequencing for quantitative and qualitative assessment of cDNA populations , 2016, Scientific Reports.

[11]  R. Serpi,et al.  Hypoxia-Inducible Factor Prolyl 4-Hydroxylase-2 Inhibition Protects Against Development of Atherosclerosis , 2016, Arteriosclerosis, thrombosis, and vascular biology.

[12]  G. Semenza,et al.  The hypoxic tumor microenvironment: A driving force for breast cancer progression. , 2016, Biochimica et biophysica acta.

[13]  A. Harris,et al.  The tumour hypoxia induced non-coding transcriptome. , 2016, Molecular aspects of medicine.

[14]  P. Ratcliffe,et al.  Pharmacological targeting of the HIF hydroxylases--A new field in medicine development. , 2016, Molecular aspects of medicine.

[15]  J. Erler,et al.  Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis. , 2016, Cancer research.

[16]  Dean P. Jones,et al.  Anticancer therapeutic potential of Mn porphyrin/ascorbate system. , 2015, Free radical biology & medicine.

[17]  P. Robbins,et al.  Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF‐2 pathway , 2015, Journal of Physiology.

[18]  P. Ratcliffe,et al.  Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer , 2015, PloS one.

[19]  P. Ratcliffe,et al.  Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain , 2015, PloS one.

[20]  M. Briehl,et al.  Manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin acts as a pro-oxidant to inhibit electron transport chain proteins, modulate bioenergetics, and enhance the response to chemotherapy in lymphoma cells. , 2015, Free radical biology & medicine.

[21]  L. Poellinger,et al.  Increased Serine-Arginine (SR) Protein Phosphorylation Changes Pre-mRNA Splicing in Hypoxia* , 2015, The Journal of Biological Chemistry.

[22]  I. Miinalainen,et al.  Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I* , 2015, The Journal of Biological Chemistry.

[23]  R. Sormunen,et al.  Muscle composition is regulated by a Lox-TGFβ feedback loop , 2015, Development.

[24]  I. Batinic-Haberle,et al.  An educational overview of the chemistry, biochemistry and therapeutic aspects of Mn porphyrins – From superoxide dismutation to H2O2-driven pathways , 2015, Redox biology.

[25]  P. Ratcliffe,et al.  Signaling hypoxia by hypoxia-inducible factor protein hydroxylases: a historical overview and future perspectives , 2014, Hypoxia.

[26]  F Buffa,et al.  Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival , 2014, Oncogene.

[27]  W. Hiatt,et al.  Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease , 2014, Vascular medicine.

[28]  C. C. West,et al.  Adipocyte Pseudohypoxia Suppresses Lipolysis and Facilitates Benign Adipose Tissue Expansion , 2014, Diabetes.

[29]  R. Blanco Sequeiros,et al.  HIF Prolyl 4-Hydroxylase-2 Inhibition Improves Glucose and Lipid Metabolism and Protects Against Obesity and Metabolic Dysfunction , 2014, Diabetes.

[30]  S. Richard,et al.  The role of PHD2 mutations in the pathogenesis of erythrocytosis , 2014, Hypoxia.

[31]  L. Heasley,et al.  Hypoxia Regulates Alternative Splicing of HIF and non-HIF Target Genes , 2014, Molecular Cancer Research.

[32]  K. Leong,et al.  SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways. , 2014, Antioxidants & redox signaling.

[33]  J. Ragoussis,et al.  Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2 , 2013, EMBO reports.

[34]  Donald Sharon,et al.  A single-molecule long-read survey of the human transcriptome , 2013, Nature Biotechnology.

[35]  M. Gassmann,et al.  Erythrocytosis: the HIF pathway in control. , 2013, Blood.

[36]  K. Sunagawa,et al.  Prolyl Hydroxylase Domain Protein 2 Plays a Critical Role in Diet-Induced Obesity and Glucose Intolerance , 2013, Circulation.

[37]  P. Ratcliffe,et al.  Pan-genomic binding of hypoxia-inducible transcription factors , 2013, Biological chemistry.

[38]  J. Myllyharju,et al.  Hypoxia-inducible Factor-1 (HIF-1) but Not HIF-2 Is Essential for Hypoxic Induction of Collagen Prolyl 4-Hydroxylases in Primary Newborn Mouse Epiphyseal Growth Plate Chondrocytes* , 2012, The Journal of Biological Chemistry.

[39]  A. Cleton-Jansen,et al.  Restoration of chemosensitivity for doxorubicin and cisplatin in chondrosarcoma in vitro: BCL-2 family members cause chemoresistance. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[40]  J. Crapo,et al.  Manganese porphyrin, MnTE-2-PyP5+, Acts as a pro-oxidant to potentiate glucocorticoid-induced apoptosis in lymphoma cells. , 2012, Free radical biology & medicine.

[41]  R. Verhaak,et al.  Transformation by the R Enantiomer of 2-Hydroxyglutarate Linked to EglN Activation , 2012, Nature.

[42]  R. Sciot,et al.  Somatic mosaic IDH1 or IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome , 2011, Nature Genetics.

[43]  Jiannis Ragoussis,et al.  High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. , 2011, Blood.

[44]  R. Klose,et al.  The oncometabolite 2‐hydroxyglutarate inhibits histone lysine demethylases , 2011, EMBO reports.

[45]  Bin Wang,et al.  Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. , 2011, Cancer cell.

[46]  B. Schierwater,et al.  The hypoxia‐inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens , 2011, EMBO reports.

[47]  B. Alman,et al.  Cartilage tumours and bone development: molecular pathology and possible therapeutic targets , 2010, Nature Reviews Cancer.

[48]  P. Hogendoorn,et al.  Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours , 2010, Histopathology.

[49]  L. Liau,et al.  Cancer-associated IDH1 mutations produce 2-hydroxyglutarate , 2009, Nature.

[50]  M. Dewhirst,et al.  Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), via suppression of oxidative stress in a mouse model of breast tumor. , 2009, Free radical biology & medicine.

[51]  E. Cummins,et al.  Hypoxia activates NF-kappaB-dependent gene expression through the canonical signaling pathway. , 2009, Antioxidants & redox signaling.

[52]  J. Mäki.  Lysyl oxidases in mammalian development and certain pathological conditions. , 2009, Histology and histopathology.

[53]  Jiannis Ragoussis,et al.  Genome-wide Association of Hypoxia-inducible Factor (HIF)-1α and HIF-2α DNA Binding with Expression Profiling of Hypoxia-inducible Transcripts , 2009, The Journal of Biological Chemistry.

[54]  Kun-Liang Guan,et al.  Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α , 2009, Science.

[55]  H. Gelderblom,et al.  The clinical approach towards chondrosarcoma. , 2008, The oncologist.

[56]  K. Arihiro,et al.  Expression of hypoxia-inducible factor-1alpha and its relationship to tumour angiogenesis and cell proliferation in cartilage tumours. , 2008, The Journal of bone and joint surgery. British volume.

[57]  J. Myllyharju.  Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets , 2008, Annals of medicine.

[58]  R. Wilkins,et al.  Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis , 2007, Pflügers Archiv - European Journal of Physiology.

[59]  K. Kivirikko,et al.  Loss of Assembly of the Main Basement Membrane Collagen, Type IV, but Not Fibril-forming Collagens and Embryonic Death in Collagen Prolyl 4-Hydroxylase I Null Mice* , 2007, Journal of Biological Chemistry.

[60]  J. Pouysségur,et al.  Hypoxia signalling in cancer and approaches to enforce tumour regression , 2006, Nature.

[61]  G. Camenisch,et al.  Integration of Oxygen Signaling at the Consensus HRE , 2005, Science's STKE.

[62]  R. Sormunen,et al.  Lysyl oxidase is essential for normal development and function of the respiratory system and for the integrity of elastic and collagen fibers in various tissues. , 2005, The American journal of pathology.

[63]  A. Harris,et al.  Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor* , 2004, Journal of Biological Chemistry.

[64]  J. Piganelli,et al.  Mechanistic analysis of the immunomodulatory effects of a catalytic antioxidant on antigen-presenting cells: implication for their use in targeting oxidation-reduction reactions in innate immunity. , 2004, Free radical biology & medicine.

[65]  G. Semenza.  Targeting HIF-1 for cancer therapy , 2003, Nature Reviews Cancer.

[66]  K. Kivirikko,et al.  Inactivation of the Lysyl Oxidase Gene Lox Leads to Aortic Aneurysms, Cardiovascular Dysfunction, and Perinatal Death in Mice , 2002, Circulation.

[67]  C. Wykoff,et al.  The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis , 1999, Nature.

[68]  W. Kaelin,et al.  Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. , 1999, Science.

[69]  I. Batinic-Haberle,et al.  Mn Porphyrin-Based Redox-Active Therapeutics , 2016 .

[70]  J. Myllyharju,et al.  Extracellular matrix genes as hypoxia-inducible targets , 2009, Cell and Tissue Research.

[71]  B. Brüne,et al.  Tumor Necrosis Factor- (cid:1) Causes Accumulation of a Ubiquitinated Form of Hypoxia Inducible Factor-1 (cid:1) through a Nuclear Factor- (cid:2) B–Dependent Pathway , 2022 .