hypoxia inducible factor 1

Summary

Summary: A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.

Top Publications

  1. Fandrey J, Gassmann M. Oxygen sensing and the activation of the hypoxia inducible factor 1 (HIF-1)--invited article. Adv Exp Med Biol. 2009;648:197-206 pubmed publisher
    ..To understand how abundance and activation of HIF-1 is regulated is of fundamental importance as it may open new therapeutic avenues to treat ischemic diseases or cancer where HIF-1 appears to be a key component of the pathophysiology. ..
  2. Clarke L, van der Kooy D. Low oxygen enhances primitive and definitive neural stem cell colony formation by inhibiting distinct cell death pathways. Stem Cells. 2009;27:1879-86 pubmed publisher
    ..Low-oxygen concentrations may be involved in expansion of early NSC populations by inhibiting cell death through different pathways in these sequential pNSC and dNSC populations. ..
  3. Shi H. Hypoxia inducible factor 1 as a therapeutic target in ischemic stroke. Curr Med Chem. 2009;16:4593-600 pubmed
    ..The author also elaborates on potential therapeutic approaches through understanding of the induction mechanism and of the potential role of HIF-1 in ischemic stroke. ..
  4. Werth N, Beerlage C, Rosenberger C, Yazdi A, Edelmann M, Amr A, et al. Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens. PLoS ONE. 2010;5:e11576 pubmed publisher
    ..Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections. ..
  5. Guo S, Miyake M, Liu K, Shi H. Specific inhibition of hypoxia inducible factor 1 exaggerates cell injury induced by in vitro ischemia through deteriorating cellular redox environment. J Neurochem. 2009;108:1309-21 pubmed publisher
    b>Hypoxia inducible factor 1 (HIF-1) has been suggested to play a critical role in the fate of cells exposed to hypoxic stress. However, the mechanism of HIF-1-regulated cell survival is still not fully understood in ischemic conditions...
  6. Xia X, Lemieux M, Li W, Carroll J, Brown M, Liu X, et al. Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A. 2009;106:4260-5 pubmed publisher
    ..These results suggest that the coordinated increase in expression of several oxygen-dependent enzymes by HIF may help compensate for decreased levels of oxygen under conditions of cellular hypoxia. ..
  7. Henchey L, Kushal S, Dubey R, Chapman R, Olenyuk B, Arora P. Inhibition of hypoxia inducible factor 1-transcription coactivator interaction by a hydrogen bond surrogate alpha-helix. J Am Chem Soc. 2010;132:941-3 pubmed publisher
    ..The synthetic helix disrupts the structure and function of this complex, resulting in a rapid downregulation of two hypoxia-inducible genes (VEGF and GLUT1) in cell culture. ..
  8. Li T, Brouwer M. Hypoxia-inducible factor, gsHIF, of the grass shrimp Palaemonetes pugio: molecular characterization and response to hypoxia. Comp Biochem Physiol B Biochem Mol Biol. 2007;147:11-9 pubmed
    ..In addition to gsHIF, we cloned a fragment of a second bHLH-PAS transcription factor from the grass shrimp, which had one bHLH and two PAS domains, and an overall 68% amino acid sequence homology with Apis mellifera trachealess protein. ..
  9. Simpson R, McKie A. Regulation of intestinal iron absorption: the mucosa takes control?. Cell Metab. 2009;10:84-7 pubmed publisher
    ..The HIF-2alpha mechanism has major effects on iron metabolism which can override the well-known hepcidin-ferroportin regulatory axis. ..

More Information

Publications62

  1. Chung J, Pasha F, Cho S, Won M, Lee J, Lee K. Pharmacophore-based 3D-QSAR of HIF-1 inhibitors. Arch Pharm Res. 2009;32:317-23 pubmed publisher
    ..929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors. ..
  2. Tang X, Zhou X, Zhou K. Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1alpha protein accumulation and vascular endothelial growth factor expression in human breast cancer cells. Acta Pharmacol Sin. 2009;30:605-16 pubmed publisher
    ..Dau inhibits human breast cancer angiogenesis by suppressing HIF-1alpha protein accumulation and VEGF expression, which may provide a novel potential mechanism for the anticancer activities of Dau in human breast cancer. ..
  3. Sakamoto T, Seiki M. A membrane protease regulates energy production in macrophages by activating hypoxia-inducible factor-1 via a non-proteolytic mechanism. J Biol Chem. 2010;285:29951-64 pubmed publisher
    ..We have thus identified a new function of MT1-MMP to mediate production of ATP so as to support energy-dependent macrophage functions by a previously unknown non-proteolytic mechanism. ..
  4. Lambert C, Roy M, Meloche J, Robitaille G, Agharazii M, Richard D, et al. Tumor necrosis factor inhibitors as novel therapeutic tools for vascular remodeling diseases. Am J Physiol Heart Circ Physiol. 2010;299:H995-1001 pubmed publisher
    ..In conclusion, we demonstrate for the first time that the inhibition of the TNF/Akt/HIF-1 axis prevents vascular remodeling. TNF inhibitors may therefore represent new and interesting therapeutic tools against VRDs. ..
  5. Semenza G. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 2010;29:625-34 pubmed publisher
  6. Rey S, Semenza G. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res. 2010;86:236-42 pubmed publisher
    ..This review will focus on the pivotal role of HIF-1 in vascular homeostasis, the involvement of HIF-1 in vascular diseases, and recent advances in targeting HIF-1 for therapy in preclinical models. ..
  7. Kimura M, Murakami T, Kizaka Kondoh S, Itoh M, Yamamoto K, Hojo Y, et al. Functional molecular imaging of ILK-mediated Akt/PKB signaling cascades and the associated role of beta-parvin. J Cell Sci. 2010;123:747-55 pubmed publisher
  8. Nizet V, Johnson R. Interdependence of hypoxic and innate immune responses. Nat Rev Immunol. 2009;9:609-17 pubmed publisher
    ..In turn, HIF-driven innate immune responses have important consequences for both the pathogen and the host, such that the tissue microenvironment fundamentally influences susceptibility to infectious disease. ..
  9. Wenger R, Camenisch G, Desbaillets I, Chilov D, Gassmann M. Up-regulation of hypoxia-inducible factor-1alpha is not sufficient for hypoxic/anoxic p53 induction. Cancer Res. 1998;58:5678-80 pubmed
  10. Semenza G. HIF-1 inhibitors for cancer therapy: from gene expression to drug discovery. Curr Pharm Des. 2009;15:3839-43 pubmed
  11. Probst Cousin S, Neundörfer B, Heuss D. Microvasculopathic neuromuscular diseases: lessons from hypoxia-inducible factors. Neuromuscul Disord. 2010;20:192-7 pubmed publisher
    ..These observations suggest that the upregulation of hypoxia-related proteins may represent an adaptation mechanism of neuromuscular tissues to immune mediated deprivation of the blood supply...
  12. Semenza G. Regulation of vascularization by hypoxia-inducible factor 1. Ann N Y Acad Sci. 2009;1177:2-8 pubmed publisher
  13. Martínez Romero R, Cañuelo A, Martinez Lara E, Javier Oliver F, Cárdenas S, Siles E. Poly(ADP-ribose) polymerase-1 modulation of in vivo response of brain hypoxia-inducible factor-1 to hypoxia/reoxygenation is mediated by nitric oxide and factor inhibiting HIF. J Neurochem. 2009;111:150-9 pubmed publisher
    ..In conclusion, our data suggest that PARP-1 has an important regulatory role in the in vivo response of brain HIF-1 to hypoxia/reoxygenation. ..
  14. Shi T, Dong Y, Li J, Gao P, Fu D, Ma D. High-throughput screening identifies CHMP4A associated with hypoxia-inducible factor 1. Life Sci. 2010;87:604-8 pubmed publisher
  15. Onnis B, Rapisarda A, Melillo G. Development of HIF-1 inhibitors for cancer therapy. J Cell Mol Med. 2009;13:2780-6 pubmed publisher
  16. Xia L, Tian D, Zhang Q, Yan W, Zhu Q, Luo M, et al. [Hypoxia induces heat shock protein HSP70-2 expression in a HIF-1 dependent manner]. Zhonghua Gan Zang Bing Za Zhi. 2009;17:207-12 pubmed
    To investigate role of hypoxia inducible factor 1 (HIF-1) in the transcriptional activation of heat shock protein 70-2 (HSP70-2) in hepatocellular carcinoma (HCC) cells under hypoxic conditions...
  17. Adams J, DiFazio L, Rolandelli R, Luján J, Haskó G, Csóka B, et al. HIF-1: a key mediator in hypoxia. Acta Physiol Hung. 2009;96:19-28 pubmed publisher
    ..The better understanding of the functions of HIF-1 and the pharmacological modulation of its activity could mean a successful therapeutic approach to these diseases. ..
  18. Li X, Sutherland S, Takeda K, Fong G, Lee F. Integrity of the prolyl hydroxylase domain protein 2:erythropoietin pathway in aging mice. Blood Cells Mol Dis. 2010;45:9-19 pubmed publisher
    ..Conversely, other Hif targets, including Vegf, Pgk1, and Phd3 are upregulated in the liver but not in the kidney in both age groups. These findings have implications for targeting this pathway in the aging. ..
  19. Anso E, Zuazo A, Irigoyen M, Urdaci M, Rouzaut A, Martinez Irujo J. Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism. Biochem Pharmacol. 2010;79:1600-9 pubmed publisher
  20. Tormos K, Chandel N. Inter-connection between mitochondria and HIFs. J Cell Mol Med. 2010;14:795-804 pubmed publisher
    ..In this review, we examine the evidence that mitochondria and HIFs are intimately connected to regulate each other resulting in appropriate responses to hypoxia. ..
  21. Gleadle J. Review article: How cells sense oxygen: lessons from and for the kidney. Nephrology (Carlton). 2009;14:86-93 pubmed publisher
    ..This understanding now generates novel therapeutic possibilities and is providing insights into the mechanisms of other renal diseases. ..
  22. Swoboda E, Strzadała L. [BNIP3 as an atypical representative of the Bcl-2 protein family. Part 2: Regulation of the expression and activity of BNIP3 protein and its role in tumorigenesis]. Postepy Hig Med Dosw (Online). 2009;63:418-24 pubmed
    ..It seems to be dependent on the stage of tumor progression. Tumor cells evolved multiple mechanisms of silencing BNIP3 expression or activity and promoter methylation is one of the most frequently observed among them ..
  23. Harten S, Ashcroft M, Maxwell P. Prolyl hydroxylase domain inhibitors: a route to HIF activation and neuroprotection. Antioxid Redox Signal. 2010;12:459-80 pubmed publisher
    ..Nevertheless, PHD inhibitors may be therapeutically useful in the treatment of stroke. Prototype PHD inhibitors have shown promising results in preclinical models. ..
  24. Kasper A, Moon E, Hu X, Park Y, Wooten C, Kim H, et al. Analysis of HIF-1 inhibition by manassantin A and analogues with modified tetrahydrofuran configurations. Bioorg Med Chem Lett. 2009;19:3783-6 pubmed publisher
    ..We have also demonstrated that the 2,3-cis-3,4-trans-4,5-cis-configuration of the tetrahydrofuran is critical to the HIF-1 inhibition of manassantin A. ..
  25. Rundqvist H, Johnson R. Hypoxia and metastasis in breast cancer. Curr Top Microbiol Immunol. 2010;345:121-39 pubmed publisher
    ..In this review we summarize the evidence for a role for hypoxic response in the biology of metastasis, with a particular emphasis on the metastasis of breast cancer and the function of the hypoxia inducible factor (HIF). ..
  26. Punchihewa C, Carver M, Yang D. DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin. Protein Sci. 2009;18:1326-31 pubmed publisher
    ..A possible base-specific interaction between DNA and topoisomerase I may be responsible for this sequence selectivity. ..
  27. Khavandi K, Khavandi A, Asghar O, Greenstein A, Withers S, Heagerty A, et al. Diabetic cardiomyopathy--a distinct disease?. Best Pract Res Clin Endocrinol Metab. 2009;23:347-60 pubmed publisher
  28. Snyder C, Chandel N. Mitochondrial regulation of cell survival and death during low-oxygen conditions. Antioxid Redox Signal. 2009;11:2673-83 pubmed publisher
    ..5-3% O2), mitochondrial oxidative stress activates hypoxia-inducible factors (HIFs) to promote cell survival. In this review, we discuss how mitochondria, BCL-2 proteins, and HIFs are crucial for cellular responses to low oxygen. ..
  29. Podar K, Anderson K. A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways. Cell Cycle. 2010;9:1722-8 pubmed
    ..Importantly, early studies already demonstrate promising preclinical of novel agents, predominantly small molecules, which target c-Myc, HIF or both. ..
  30. Isoe T, Makino Y, Mizumoto K, Sakagami H, Fujita Y, Honjo J, et al. High glucose activates HIF-1-mediated signal transduction in glomerular mesangial cells through a carbohydrate response element binding protein. Kidney Int. 2010;78:48-59 pubmed publisher
    ..Our results show that ChREBP and HIF-1alpha mediate gene regulation in mesangial cells. Further studies will be needed to find out whether these findings are relevant to the development of the diabetic nephropathy. ..
  31. Safronova O, Morita I. Transcriptome remodeling in hypoxic inflammation. J Dent Res. 2010;89:430-44 pubmed publisher
    ..Furthermore, this review discusses the molecular cross-talk between glucocorticoid anti-inflammatory pathways and hypoxia. ..
  32. Singh V, Singh S. Progressive tumor growth-associated altered tumor microenvironment: implications in a tumor stage-dependent modulation in survival of a murine T cell lymphoma. J Cancer Res Clin Oncol. 2009;135:1015-24 pubmed publisher
  33. Yang R, Shaufl A, Killeen M, Fink M. Ethyl pyruvate ameliorates liver injury secondary to severe acute pancreatitis. J Surg Res. 2009;153:302-9 pubmed publisher
    ..EP treatment also significantly improved body circulating blood volume. EP is a potent anti-inflammatory and anti-oxidative agent to ameliorate hepatic local inflammatory response and resultantly decreases liver injury secondary to SAP. ..
  34. Ahmad I, Britigan B, Abdalla M. Oxidation of thiols and modification of redox-sensitive signaling in human lung epithelial cells exposed to Pseudomonas pyocyanin. J Toxicol Environ Health A. 2011;74:43-51 pubmed publisher
    ..Data indicate that pyocyanin-induced alterations in mitochondrial and cytosolic thiols, as well as oxidant-sensitive proteins, may contribute to P. aeruginosa-mediated lung injury. ..
  35. McCarty M, Barroso Aranda J, Contreras F. Oxidative stress therapy for solid tumors - a proposal. Med Hypotheses. 2010;74:1052-4 pubmed publisher
    ..Cell culture studies could be employed to devise effective protocols that could be tested in xenografted rodents and, ultimately, in exploratory clinical trials. ..
  36. Siddiq A, Aminova L, Troy C, Suh K, Messer Z, Semenza G, et al. Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathways. J Neurosci. 2009;29:8828-38 pubmed publisher
  37. Zhu G, Tang Y, Liang X, Zheng M, Yang J, Zhou H, et al. Role of hypoxia-inducible factor-1 alpha in the regulation of plasminogen activator activity in rat knee joint chondrocytes. Osteoarthritis Cartilage. 2009;17:1494-502 pubmed publisher
    ..The inhibition of HIF-1alpha in the PA activity of articular chondrocytes probably plays an important role in the maintenance of articular cartilage matrix. ..
  38. Hu Y, Kirito K, Yoshida K, Mitsumori T, Nakajima K, Nozaki Y, et al. Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan. Mol Cancer Ther. 2009;8:2329-38 pubmed publisher
    ..We conclude that HIF-1 inhibition may be an attractive therapeutic strategy for multiple myeloma. ..
  39. Kizaka Kondoh S, Itasaka S, Zeng L, Tanaka S, Zhao T, Takahashi Y, et al. Selective killing of hypoxia-inducible factor-1-active cells improves survival in a mouse model of invasive and metastatic pancreatic cancer. Clin Cancer Res. 2009;15:3433-41 pubmed publisher
  40. Greenfield J, Cobb W, Lyden D. Resisting arrest: a switch from angiogenesis to vasculogenesis in recurrent malignant gliomas. J Clin Invest. 2010;120:663-7 pubmed publisher
  41. Kizaka Kondoh S, Tanaka S, Harada H, Hiraoka M. The HIF-1-active microenvironment: an environmental target for cancer therapy. Adv Drug Deliv Rev. 2009;61:623-32 pubmed publisher
    ..Therefore targeting strategies to overcome the HIF-1-active microenvironment are important for cancer therapy. ..
  42. Mardilovich K, Shaw L. Hypoxia regulates insulin receptor substrate-2 expression to promote breast carcinoma cell survival and invasion. Cancer Res. 2009;69:8894-901 pubmed publisher
    ..Collectively, our results reveal a novel mechanism by which IRS-2 contributes to the aggressive behavior of hypoxic tumor cells. ..
  43. Tennant D, Frezza C, MacKenzie E, Nguyen Q, Zheng L, Selak M, et al. Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene. 2009;28:4009-21 pubmed publisher
    ..We also show that derivatized alpha-ketoglutarate can permeate multiple layers of cells, reducing HIF1alpha levels and its target genes in vivo. ..
  44. Nakamura H, Yamazaki M, Ohyama T, Inoue T, Arakawa N, Domon Y, et al. Role of angiotensin II type 1 receptor on retinal vascular leakage in a rat oxygen-induced retinopathy model. Ophthalmic Res. 2009;41:210-5 pubmed publisher
    ..These results suggest that the AT1 receptor is, at least partly, responsible for hyperpermeability in the OIR rat retina via a mechanism independent of HIF-1 and VEGF expression. ..
  45. Pasanen A, Heikkilä M, Rautavuoma K, Hirsilä M, Kivirikko K, Myllyharju J. Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. Int J Biochem Cell Biol. 2010;42:1189-200 pubmed publisher
    ..A further level of regulation is brought about by the fact that the levels of the HIF-3alpha transcripts themselves are regulated by hypoxia and by changes in HIF-1 levels. ..
  46. Park J, Jeong J, Kang M, Baek J, Shin J, Lee S, et al. Inhibition of the PI3K-Akt pathway suppresses sFlt1 expression in human placental hypoxia models in vitro. Placenta. 2010;31:621-9 pubmed publisher
    ..This pathway provides a potential target for a new treatment strategy in patients with pre-eclampsia. ..
  47. Morgan J, Mahdi F, Liu Y, Coothankandaswamy V, Jekabsons M, Johnson T, et al. The marine sponge metabolite mycothiazole: a novel prototype mitochondrial complex I inhibitor. Bioorg Med Chem. 2010;18:5988-94 pubmed publisher
    ..The exquisite potency and structural novelty of 1 suggest that it may serve as a valuable molecular probe for mitochondrial biology and HIF-mediated hypoxic signaling...
  48. Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem. 2009;107:1053-62 pubmed publisher
    ..In this review, we will first introduce the cellular responses to hypoxia and HIF-1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers. ..
  49. Hoenig M, Bianchi C, Rosenzweig A, Sellke F. Decreased vascular repair and neovascularization with ageing: mechanisms and clinical relevance with an emphasis on hypoxia-inducible factor-1. Curr Mol Med. 2008;8:754-67 pubmed
    ..We suggest that exercise, Cobalt compounds or hydralazine may reverse the age-related decline by up-regulating HIF-1-mediated signaling. ..
  50. Dehne N, Brüne B. HIF-1 in the inflammatory microenvironment. Exp Cell Res. 2009;315:1791-7 pubmed publisher
    ..This review summarizes mechanisms of HIF activation in mammalian immune cells, especially in macrophages and neutrophils, and outlines how HIF moderates inflammation. ..
  51. Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol. 2009;8:398-412 pubmed publisher
    ..We also discuss whether preconditioning and tolerance occur naturally in the brain and assess the most promising candidate strategies that are being investigated. ..
  52. Illsley N, Caniggia I, Zamudio S. Placental metabolic reprogramming: do changes in the mix of energy-generating substrates modulate fetal growth?. Int J Dev Biol. 2010;54:409-19 pubmed publisher
  53. Ferreira L, Gerecht S, Fuller J, Shieh H, Vunjak Novakovic G, Langer R. Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells. Biomaterials. 2007;28:2706-17 pubmed
    ..Functionalized dextran-based hydrogels could thus enable derivation of vascular cells in large quantities, particularly endothelial cells, for potential application in tissue engineering and regenerative medicine. ..