CoChat
Sign Up
Cited by 45Cancer, Hypoxia, and MetabolismNitric Oxide and Endothelin EffectsAngiogenesis and VEGF in Cancer

Crosstalk between nitric oxide and hypoxia-inducible factor signaling pathways: an update

Open access
Poyton, Robert, Hendrickson, Marina·2015·Research and Reports in Biochemistry
DOI 10.2147/rrbc.s58280
Open this paper in CoChat — free accountOpen PDF

Abstract

Abstract: Hypoxia-inducible factor-1 (HIF-1) is responsible for cellular adaptations to hypoxia. While oxygen (O 2 ) negatively regulates its stability, many other factors affect HIF-1 stability and activity, including nitric oxide (NO). NO derived from l-arginine and nitrite (NO 2 – ) could nitrosylate or nitrate HIF-1 and multiple proteins involved in HIF-1 regulation, and can allow HIF-1 to escape normoxic degradation. In turn, HIF-1 can increase NO production through multiple mechanisms, including increased inducible nitric oxide synthase (iNOS) expression and subunit 4-2 of cytochrome c oxidase (COX4-2) expression. There is therefore a high degree of crosstalk between HIF-1 and NO signaling. As such, many cellular responses to NO are mediated by HIF-1, and vice versa. This includes, but is not limited to, angiogenesis, apoptosis, senescence, and metabolic changes. These pathways all have important functions in normal physiology and when altered can contribute or, in some cases, lead to pathogenesis. Keywords: HIF, nitric oxide, Cco/NO mitochondrial signaling, ROS/RNS, cancer

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2147/rrbc.s58280

Cites

18 of 18 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • HIF-2α, HIF-3α, ARNT2, and ARNTL exhibit pronounced cell type- and tissue-specific expression patterns.

    “In contrast, HIF-2α, HIF-3α, ARNT2, and ARNTL exhibit pronounced cell type– and tissue-specific expression patterns [29,63,64]”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [64]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 92

  1. Semenza G, Wang G. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992;12: 5447.
  2. Wang G, Jiang B, Rue E, Semenza G. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O 2 tension. Proc Natl Acad Sci U S A. 1995;92:5510-5514.
  3. Takahata S, Sogawa K, Kobayashi A, et al. Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock. Biochem Biophys Res Commun. 1998;248: 789-794.
  4. Sena J, Wang L, Heasley L, Hu C. Hypoxia regulates alternative splic- ing of HIF and non-HIF target genes. Mol Cancer Res. 2014;12(9): 1233-1243.
  5. Makino Y, Kanopka A, Wilson W, Tanaka H, Poellinger L. Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3α locus. J Biol Chem. 2002;277(36): 32405-32408.
  6. Maltepe E, Keith B, Arsham A, Brorson J, Simon M. The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia. Biochem Biophys Res Commun. 2000;273:231-238.
  7. Ruas J, Poellinger L, Pereira T. Functional Analysis of Hypoxia- inducible Factor-1α-mediated transactivation: identification of amino acid residues critical for transcriptional activation and/or interaction with Creb-binding protein. J Biol Chem. 2002;277:38723-38730.
  8. Kewley R, Whitelaw M, Chapman-Smith A. The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol. 2004;36:189-204.
  9. Wiesener M, Jürgensen J, Rosenberger C, et al. Widespread hypoxia- inducible expression of HIF-2α in distinct cell populations of different organs. FASEB J. 2003;17:271-273.
  10. Ikeda M, Nomura M. cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identi- fication of alternatively spliced variants with alternative translation initiation site usage. Biochem Biophys Res Commun. 1997;233: 258-264.
  11. Mole D, Blancher C, Copley R, et al. Genome-wide association of hypoxia-inducible factor (HIF)-1α and HIF-2α DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem. 2009;284(25):16767-16775.
  12. Semenza G. HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev. 2010;20:51-56.
  13. Scortegagna M, Ding K, Zhang Q, et al. HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood. 2005;105:3133-3140.
  14. Ratcliffe P. HIF-1 and HIF-2: working alone or together in hypoxia? J Clin Invest. 2007;117:862-865.
  15. Makino Y, Cao R, Svensson K, et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature. 2001;414(6863):550-554.
  16. Jaakkola P, Mole D, Tian Y, et al. Targeting of HIF-α to the von Hippel- Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001;292(5516):468-472.
  17. Maxwell P, Wiesener M, Chang G, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399(6733):271-275.
  18. Paltoglou S, Roberts B. HIF-1α and EPAS ubiquitination mediated by the VHL tumour suppressor involves flexibility in the ubiquit- ination mechanism, similar to other RING E3 ligases. Oncogene. 2006;26:604-609.
  19. Zhang N, Fu Z, Linke S, et al. The asparaginyl hydroxylase factor inhibiting HIF-1α is an essential regulator of metabolism. Cell Metab. 2010;11:364-378.
  20. Masson N, Singleton R, Sekirnik R, et al. The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity. EMBO Rep. 2012;13:251-257.
  21. Semenza G. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest. 2013;123:3664-3671.
  22. Carroll V, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1α versus HIF-2α in the regulation of HIF target genes in response to hypoxia, insu- lin-like growth factor-I, or loss of von Hippel-Lindau function: implica- tions for targeting the HIF pathway. Cancer Res. 2006;66:6264-6270.
  23. Jung F, Palmer L, Zhou N, Johns R. Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes. Circ Res. 2000;86:319-325.
  24. Kim J, Tchernyshyov I, Semenza G, Dang C. HIF-1-mediated expres- sion of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177185.
  25. Huang D, Li T, Li X, et al. HIF-1-mediated suppression of acyl- CoA dehydrogenases and fatty acid oxidation is critical for cancer progression. Cell Rep. 2014;25(8):1930-1942.
  26. Zhang H, Bosch-Marce M, Shimoda L, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 2008;283:10892-10903.
  27. Jiang B, Agani F, Passaniti A, Semenza G. V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res. 1997;57(23):5328-5335.
  28. Eliceiri B, Paul R, Schwartzberg P, Hood J, Leng J, Cheresh D. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell. 1999;4:915-924.
  29. Mukhopadhyay D, Tsiokas L, Zhou X, Foster D, Brugge J, Sukhatme V. Hypoxic induction of human vascular endothelial growth factor expres- sion through c-Src activation. Nature. 1995;375(6532):577-581.
  30. Gray M, Zhang J, Ellis L, et al. HIF-1α, STAT3, CBP/p300 and Ref-1/ APE are components of a transcriptional complex that regulates Src- dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene. 2005;24:3110-3120.
  31. Moncada S, Palmer R, Higgs E. Nitric oxide: physiology, pathophysiol- ogy, and pharmacology. Pharmacol Rev. 1991;43:109-142.
  32. Ball K, Nelson A, Foster D, Poyton R. Nitric oxide produced by cyto- chrome c oxidase helps stabilize HIF-1α in hypoxic mammalian cells. Biochem Biophys Res Commun. 2012;420:727-732.
  33. Poyton R, Ball K, Castello P. Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab. 2009;20:332-340.
  34. Benhar M, Stamler J. A central role for S-nitrosylation in apoptosis. Nat Cell Biol. 2005;7:645-646.
  35. Castello P, David P, McClure T, Crook Z, Poyton R. Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes. Cell Metab. 2006;3:277-287.
  36. Liu L, Yan Y, Zeng M, et al. Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell. 2004;116:617-628.
  37. Hara M, Agrawal N, Kim S, et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005;7:665-674.
  38. Alderton W, Cooper C, Knowles R. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357:593.
  39. Zweier J, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med. 1995;1: 804-809.
  40. van Faassen E, Bahrami S, Feelisch M, et al. Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev. 2009;29: 683-741.
  41. Vitturi D, Patel R. Current perspectives and challenges in understand- ing the role of nitrite as an integral player in nitric oxide biology and therapy. Free Radical Biol Med. 2011;51:805-812.
  42. Poyton R, Ball K. Therapeutic photobiomodulation: nitric oxide and a novel function of mitochondrial cytochrome C oxidase. Discov Med. 2011;11:154-159.
  43. Hematian S, Siegler M, Karlin K. Heme/copper assembly mediated nitrite and nitric oxide interconversion. J Am Chem Soc. 2012;134: 18912-18915.
  44. Ball K, Castello P, Poyton R. Low intensity light stimulates nitrite- dependent nitric oxide synthesis but not oxygen consumption by cytochrome c oxidase: implications for phototherapy. J Photochem Photobiol B. 2011;102:182-191.
  45. Li B, Skinner C, Castello P, et al. Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respi- ratory chain and nitric oxide levels. J Aging Res. 2011;2011:1-16.
  46. Poyton R, Castello P, Ball K, Woo D, Pan N. Mitochondrial nitrite- dependent NO production and hypoxic signaling. Ann N Y Acad Sci. 2009;1177:48-56.
  47. Castello P, Woo D, Ball K, Wojcik J, Liu L, Poyton R. Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling. Proc Natl Acad Sci U S A. 2008;105:8203-8208.
  48. Burke P, Poyton R. Structure/function of oxygen-regulated isoforms in cytochrome c oxidase. J Exp Biol. 1998;201:1163-1175.
  49. Ray P, Huang B, Tsuji Y. Reactive oxygen species (ROS) homeosta- sis and redox regulation in cellular signaling. Cell Signal. 2012;24: 981-990.
  50. Schieber M, Chandel N. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24:R453-R462.
  51. Finkel T. Signal transductants by mitochondrial oxidants. J Biol Chem. 2012;297:4434-4440.
  52. Hoffman D, Brookes P. Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic Conditions. J Biol Chem. 2009;284:16236-16245.
  53. Chowdhury R, Godoy L, Thiantanawat A, Trudel L, Deen W, Wogan G. Nitric oxide produced endogenously is responsible for hypoxia-induced HIF-1α stabilization in colon carcinoma cells. Chem Res Toxicol. 2012;25:2194-2202.
  54. Huang L, Willmore W, Gu J, Goldberg M, Bunn H. Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide: implications for oxygen sensing and signaling. J Biol Chem. 1999;274:9038-9044.
  55. Sandau K. Accumulation of HIF-1α under the influence of nitric oxide. Blood. 2001;97:1009-1015.
  56. Caneba C, Yang L, Baddour J, et al. Nitric oxide is a positive regulator of the Warburg effect in ovarian cancer cells. Cell Death Dis. 2014;5: e1302.
  57. Kuwabara M, Kakinuma Y, Ando M, et al. Nitric oxide stimulates vas- cular endothelial growth factor production in cardiomyocytes involved in angiogenesis. Jpn J Physiol. 2006;56:95-101.
  58. Sharifpanah F, Saliu F, Bekhite M, Wartenberg M, Sauer H. β-adrenergic receptor antagonists inhibit vasculogenesis of embryonic stem cells by downregulation of nitric oxide generation and interference with VEGF signaling. Cell Tissue Res. 2014;358:443-452.
  59. Berchner-Pfannschmidt U, Tug S, Kirsch M, Fandrey J. Oxygen-sensing under the influence of nitric oxide. Cell Signal. 2010;22:349-356.
  60. Li F, Sonveaux P, Rabbani Z, et al. Regulation of HIF-1α stability through S-nitrosylation. Mol Cell. 2007;26:63-74.
  61. Yasinska I, Sumbayev V. S-nitrosation of Cys-800 of HIF-1α protein activates its interaction with p300 and stimulates its transcriptional activity. FEBS Lett. 2003;549:105-109.
  62. Cho H, Ahn D, Park H, Yang E. Modulation of p300 binding by post- translational modifications of the C-terminal activation domain of hypoxia-inducible factor-1α. FEBS Lett. 2007;581:1542-1548.
  63. Chowdhury R, Flashman E, Mecinović J, et al. Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1). J Mol Biol. 2011;410:268-279.
  64. Park Y, Ahn D, Oh M, et al. Nitric oxide donor, (±)-S-nitroso-N- acetylpenicillamine, stabilizes transactive hypoxia-inducible factor-1 by inhibiting von Hippel-Lindau recruitment and asparagine hydroxylation. Mol Pharmacol. 2008;74:236-245.
  65. Palmer L, Doctor A, Chhabra P, et al. S-nitrosothiols signal hypoxia- mimetic vascular pathology. J Clin Invest. 2007;117:2592-2601.
  66. Liu H, Yu S, Zhang H, Xu J. Identification of nitric oxide as an endog- enous inhibitor of 26S proteasomes in vascular endothelial cells. PLoS One. 2014;9:e98486.
  67. Hudson C, Liu M, Chiang G, et al. Regulation of hypoxia-inducible fac- tor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol. 2002;22:7004-7014.
  68. Zhou J. PI3K/Akt is required for heat shock proteins to protect hypoxia- inducible factor 1 from pVHL-independent degradation. J Biol Chem. 2004;279:13506-13513.
  69. Zeiher A, Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399:601-605.
  70. Datta K, Li J, Bhattacharya R, Gasparian L, Wang E, Mukhopadhyay D. Protein kinase c transactivates hypoxia-inducible factor by promoting its association with p300 in renal cancer. Cancer Res. 2004;64:456-462.
  71. Geng H, Liu Q, Xue C, et al. HIF1 protein stability is increased by acetylation at lysine 709. J Biol Chem. 2012;287:35496-35505.
  72. Arif M, Vedamurthy B, Choudhari R, et al. Nitric oxide-mediated histone hyperacetylation in oral cancer: target for a water-soluble HAT inhibitor, CTK7A. Chem Biol. 2010;17:903-913.
  73. Kornberg M, Sen N, Hara M, et al. GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol. 2010;12:1094-1100.
  74. Lim J, Lee Y, Chun Y, Chen J, Kim J, Park J. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1α. Mol Cell. 2010;38:864-878.
  75. Laemmle A, Lechleiter A, Roh V, et al. Inhibition of SIRT1 impairs the accumulation and transcriptional activity of HIF-1α protein under hypoxic conditions. PLoS One. 2012;7:e33433.
  76. Mylonis I, Chachami G, Samiotaki M, et al. Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1. J Biol Chem. 2006;281:33095-33106.
  77. Callsen D, Pfeilschifter J, Brüne B. Rapid and delayed p42/p44 mitogen- activated protein kinase activation by nitric oxide: the role of cyclic GMP and tyrosine phosphatase inhibition. J Immunol. 1998;161: 4852-4858.
  78. Fukuda R, Zhang H, Kim J, Shimoda L, Dang C, Semenza G. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respira- tion in hypoxic cells. Cell. 2007;129:111-122.
  79. Iyer N, Kotch L, Agani F, et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1alpha. Genes Dev. 1998;12:149-162.
  80. Simon M, Keith B. The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol. 2008;9: 285-296.
  81. Mustafa R, Ahmed S, Gupta A, Venuto R. A comprehensive review of hypertension in pregnancy. J Pregnancy. 2012;2012:1-19.
  82. Cowburn A, Alexander L, Southwood M, Nizet V, Chilvers E, Johnson R. Epidermal deletion of HIF-2a stimulates wound closure. J Invest Dermatol. 2014;134:801-808.
  83. Luo J, Chen A. Nitric oxide: a newly discovered function on wound healing. Acta Pharmacol Sin. 2005;26:259-264.
  84. Yang L, Guo X, Du C, et al. Interleukin-1 beta increases activity of human endothelial progenitor cells: involvement of PI3K-Akt signaling pathway. Inflammation. 2012;35:1242-1250.
  85. Akama K, Van Eldik L. β-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta -and tumor necrosis factor- alpha (TNFα)-dependent, and involves a TNFα receptor-associated factor-and NFκ B-inducing kinase-dependent signaling mechanism. J Biol Chem. 2000;275:7918-7924.
  86. Johnson M, Grazul-Bilska A, Redmer D, Reynolds L. Effects of estradiol-17β on expression of mRNA for seven angiogenic factors and their receptors in the endometrium of ovariectomized (OVX) ewes. Endocrinology. 2006;30:333-342.
  87. Reynolds L, Grazul-Bilska A, Redmer D. Angiogenesis in the female reproductive organs: pathological implications. Int J Exp Pathol. 2002;83:151-164.
  88. Hirota K, Fukuda R, Takabuchi S, et al. Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling. J Biol Chem. 2004;279:41521-41528. 100. Wei H, Bedja D, Koitabashi N, et al. Endothelial expression of hypoxia- inducible factor 1 protects the murine heart and aorta from pressure overload by suppression of TGF-signaling. Proc Natl Acad Sci U S A. 2012;109:E841-E850. 101. Sano M, Minamino T, Toko H, et al. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature. 2007;446:444-448. 102. Cheng S, Quintin J, Cramer R, et al. mTOR-and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014;345:1250684. 103. Peyssonnaux C, Datta V, Cramer T, et al. HIF-1α expression regulates the bactericidal capacity of phagocytes. J Clin Invest. 2005;115: 1806-1815. 104. Elks P, Brizee S, van der Vaart M, et al. Hypoxia inducible fac- tor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism. PLoS Pathog. 2013;9: e1003789. 105.
  89. Herbst S, Schaible U, Schneider B. Interferon gamma activated mac- rophages kill mycobacteria by nitric oxide induced apoptosis. PLoS One. 2011;6:e19105. 106. Guo K, Searfoss G, Krolikowski D, et al. Hypoxia induces the expres- sion of the pro-apoptotic gene BNIP3. Cell Death Differ. 2001;8: 367-376. 107. Zamora R, Vodovotz Y, Betten B, et al. Intestinal and hepatic expres- sion of BNIP3 in necrotizing enterocolitis: regulation by nitric oxide and peroxynitrite. Am J Physiol Gastrointest Liver Physiol. 2005;289: G822-G830. 108.
  90. Koshiji M, Kageyama Y, Pete E, Horikawa I, Barrett J, Huang L. HIF-1α induces cell cycle arrest by functionally counteracting Myc. EMBO J. 2004;23:1949-1956. 128.
  91. Krick S, Eul B, Hänze J, et al. Role of hypoxia-inducible factor-1α in hypoxia-induced apoptosis of primary alveolar epithelial type II cells. Am J Respir Cell Mol Biol. 2005;32:395-403. 129.
  92. Soucek T, Cumming R, Dargusch R, Maher P, Schubert D. The regu- lation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide. Neuron. 2003;39:43-56. 145. Miller G, Tennille P, Morgan A, et al. Acute effect of a high nitrate diet on brain perfusion in older adults. Nitric Oxide. 2011;24:S28. 146. Näpänkangas J, Liimatta E, Joensuu P, Bergmann U, Ylitalo K, Hassinen I. Superoxide production during ischemia-reperfusion in the perfused rat heart: a comparison of two methods of measurement. J Mol Cell Cardiol. 2012;53:906-915. 147. Halkos M, Kerendi F, Corvera J, et al. Myocardial protection with postconditioning is not enhanced by ischemic preconditioning. Ann Thorac Surg. 2004;78:961-969. 148. Gulati P, Singh N. Evolving possible link between PI3K and NO pathways in neuroprotective mechanism of ischemic postconditioning in mice. Mol Cell Biochem. 2014;397:255-265. 149. Mahfoudh-Boussaid A, Zaouali M, Hadj-Ayed K, et al. Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide. J Biomed Sci. 2012;19:7. 150. Cai Z, Zhong H, Bosch-Marce M, et al. Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial defi- ciency of HIF-1. Cardiovasc Res. 2007;77:463-470. 151. Semenza G. Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochin Biophys Acta. 2011;1813:1263-1268. 152. Witte M, Thornton F, Tantry U, Barbul A. l-arginine supplementation enhances diabetic wound healing: Involvement of the nitric oxide synthase and arginase pathways. Metabolism. 2002;51:1269-1273. 153. Bin-Jaliah I, El-Attar S, Khaleel E, El-Sayed L, Haidara M. Remedial effects of vitamin E and L-arginine on peripheral neuropathy in streptozotocin-induced diabetic rats. Am J Pharmacol Toxicol. 2014;9: 13-23. 154. Simo R, Sundstrom J, Antonetti D. Ocular anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care. 2014;37:893-899. 155. Olson E, Demopoulos L, Haws T, 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. Vasc Med. 2014;19:473-482. 156. Reischl S, Li L, Walkinshaw G, Flippin L, Marti H, Kunze R. Inhibition of HIF prolyl-4-hydroxylases by FG-4497 reduces brain tissue injury and edema formation during ischemic Stroke. PLoS One. 2014;9: e84767. 157. Karuppagounder S, Ratan R. Hypoxia-inducible factor prolyl hydroxylase inhibition: robust new target or another big bust for stroke therapeutics? J Cereb Blood Flow Metab. 2012;32:1347-1361. 158. Casanovas O, Hicklin D, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005;8:299-309. 159. Keunen O, Johansson M, Oudin A, et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci U S A. 2011;108:3749-3754. 160.

Cited by

Sorted by citations

Authors
Poyton, R., & Hendrickson, M.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Hendrickson, Marina
Venue
Research and Reports in Biochemistry
Publisher
Informa UK Limited
Published
2015-06
Pages
147
ISSN
2230-3154 (ISSN-L)
DOI
10.2147/rrbc.s58280
OpenAlex
W1865957328
Cited by
45
References
18
Citations by year
2026: 2 · 2025: 3 · 2024: 11 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 1 · 2017: 3 · 2015: 1
FWCI
0.55
Type
journal article
Language
en
Open access
Licence
Locations
Research and Reports in Biochemistry (publishedVersion, cc-by-nc)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
nitric oxide, HIF-1, HIF-1 signaling, nitrosylation, inducible nitric oxide synthase, mitochondrial signaling, reactive oxygen species, reactive nitrogen species, angiogenesis, apoptosis, cellular senescence, cancer, hypoxia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review