alpha subunit hypoxia inducible factor 1


Summary: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.

Top Publications

  1. Brouwer E, Gouw A, Posthumus M, van Leeuwen M, Boerboom A, Bijzet J, et al. Hypoxia inducible factor-1-alpha (HIF-1alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis. Clin Exp Rheumatol. 2009;27:945-51 pubmed
    ..These results thus suggest that HIF-1alpha could serve as an important new therapeutic target in RA, targeting both angiogenesis and inflammation. ..
  2. Villaume K, Blanc M, Gouysse G, Walter T, Couderc C, Nejjari M, et al. VEGF secretion by neuroendocrine tumor cells is inhibited by octreotide and by inhibitors of the PI3K/AKT/mTOR pathway. Neuroendocrinology. 2010;91:268-78 pubmed publisher
  3. Knechtel G, Szkandera J, Stotz M, HOFMANN G, Langsenlehner U, Krippl P, et al. Single nucleotide polymorphisms in the hypoxia-inducible factor-1 gene and colorectal cancer risk. Mol Carcinog. 2010;49:805-9 pubmed publisher
    ..We conclude that functional polymorphisms in the HIF1A gene do not modify CRC risk but maybe associated with clinic-pathological features of the disease. ..
  4. Spinella F, Rosanò L, Del Duca M, Di Castro V, Nicotra M, Natali P, et al. Endothelin-1 inhibits prolyl hydroxylase domain 2 to activate hypoxia-inducible factor-1alpha in melanoma cells. PLoS ONE. 2010;5:e11241 pubmed publisher
    ..These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability. ..
  5. Henze A, Riedel J, Diem T, Wenner J, Flamme I, Pouyseggur J, et al. Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback regulators of hypoxia-inducible factors. Cancer Res. 2010;70:357-66 pubmed publisher
  6. Miyazawa M, Yasuda M, Fujita M, Hirabayashi K, Hirasawa T, Kajiwara H, et al. Granulosa cell tumor with activated mTOR-HIF-1alpha-VEGF pathway. J Obstet Gynaecol Res. 2010;36:448-53 pubmed publisher
    ..It was concluded that mTOR-targeted therapy may represent a promising strategy for some GCT with an activated mTOR-HIF-1alpha-VEGF pathway...
  7. Goteri G, Lucarini G, Zizzi A, Rubini C, Di Primio R, Tranquilli A, et al. Proangiogenetic molecules, hypoxia-inducible factor-1alpha and nitric oxide synthase isoforms in ovarian endometriotic cysts. Virchows Arch. 2010;456:703-10 pubmed publisher
    ..The therapeutic target would be mainly the capsular vasculature, more than the vasculature of ectopic endometrial tissues. ..
  8. Zhang D, Li J, Costa M, Gao J, Huang C. JNK1 mediates degradation HIF-1alpha by a VHL-independent mechanism that involves the chaperones Hsp90/Hsp70. Cancer Res. 2010;70:813-23 pubmed publisher
    ..Taken together, our studies define a novel function for JNK1 in regulating HIF-1alpha turnover by a VHL-independent mechanism. ..
  9. Narita T, Yin S, Gelin C, Moreno C, Yepes M, Nicolaou K, et al. Identification of a novel small molecule HIF-1alpha translation inhibitor. Clin Cancer Res. 2009;15:6128-36 pubmed publisher
    ..These results show that KC7F2 is a potent HIF-1 pathway inhibitor and its potential as a cancer therapy agent warrants further study. ..

More Information


  1. Duval E, Leclercq S, Elissalde J, Demoor M, Galera P, Boumediene K. Hypoxia-inducible factor 1alpha inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III c. Arthritis Rheum. 2009;60:3038-48 pubmed publisher
    ..This suggests that manipulation of HIF-1alpha could represent a promising approach to the treatment of osteoarthritis. ..
  2. van De Sluis B, Groot A, Vermeulen J, van der Wall E, van Diest P, Wijmenga C, et al. COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70. PLoS ONE. 2009;4:e7332 pubmed publisher
    ..These data reveal a novel role for COMMD1 in conjunction with HSP90beta/HSP70 in the ubiquitin and O(2)-independent regulation of HIF-1alpha. ..
  3. Molitoris K, Kazi A, Koos R. Inhibition of oxygen-induced hypoxia-inducible factor-1alpha degradation unmasks estradiol induction of vascular endothelial growth factor expression in ECC-1 cancer cells in vitro. Endocrinology. 2009;150:5405-14 pubmed publisher
    ..Through the induction of increased microvascular permeability and the consequent exudation of plasma growth factors, VEGF in turn may play an essential role in cancer cell proliferation in vivo. ..
  4. Baranello L, Bertozzi D, Fogli M, Pommier Y, Capranico G. DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1alpha gene locus. Nucleic Acids Res. 2010;38:159-71 pubmed publisher
    ..A changed balance of antisense transcripts and mRNAs may then lead to altered regulation of HIF-1alpha activity in human cancer cells. ..
  5. Koh M, Spivak Kroizman T, Powis G. Inhibiting the hypoxia response for cancer therapy: the new kid on the block. Clin Cancer Res. 2009;15:5945-6 pubmed publisher
    ..Here, we discuss the proposed mechanism of action of KC7F2 and its potential strengths and limitations in comparison with other promising HIF-1alpha inhibitors. ..
  6. Nys K, Van Laethem A, Michiels C, Rubio N, Piette J, Garmyn M, et al. A p38(MAPK)/HIF-1 pathway initiated by UVB irradiation is required to induce Noxa and apoptosis of human keratinocytes. J Invest Dermatol. 2010;130:2269-76 pubmed publisher
  7. Diebold I, Petry A, Djordjevic T, BelAiba R, Fineman J, Black S, et al. Reciprocal regulation of Rac1 and PAK-1 by HIF-1alpha: a positive-feedback loop promoting pulmonary vascular remodeling. Antioxid Redox Signal. 2010;13:399-412 pubmed publisher
  8. Torres O, Palomino Morales R, Vazquez Rodriguez T, Gamallo C, Miranda Filloy J, Amigo Diaz E, et al. Lack of association between hypoxia inducible factor-1 alpha gene polymorphisms and biopsy-proven giant cell arteritis. Clin Exp Rheumatol. 2010;28:40-5 pubmed
    ..1%) compared to the remaining GCA patients (22.8%); OR 1.60 (95% CI: 0.81- 3.16); p=0.18. Our results do not confirm an implication of HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA. ..
  9. Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti C, et al. ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell. 2010;17:319-32 pubmed publisher
    ..Importantly, this mechanism is manifested in high Gleason grade cancers, which exhibit significantly more HIF-1alpha and VEGF expression, and Snail1 nuclear localization compared to low Gleason grade cancers. ..
  10. Fu Y, Huang R, Du J, Yang R, An N, Liang A. Glioma-derived mutations in IDH: from mechanism to potential therapy. Biochem Biophys Res Commun. 2010;397:127-30 pubmed publisher
  11. Jusman S, Halim A, Wanandi S, Sadikin M. Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) related to oxidative stress in liver of rat-induced by systemic chronic normobaric hypoxia. Acta Med Indones. 2010;42:17-23 pubmed
    ..Systemic hypoxia induction caused increased ROS formation during hypoxia, and depleted the GSH concentration in the liver. Oxidative stress present in liver of rat was induced by systemic hypoxia. ..
  12. Saini Y, Greenwood K, Merrill C, Kim K, Patial S, Parameswaran N, et al. Acute cobalt-induced lung injury and the role of hypoxia-inducible factor 1alpha in modulating inflammation. Toxicol Sci. 2010;116:673-81 pubmed publisher
    ..The timing of these results suggests that the loss of epithelial-derived HIF1alpha alters the lung's innate immune response and biases the tissue toward a Th2-mediated inflammation. ..
  13. Zhang J, Wu H, Wang L, Tian Y, Zhang J, Wu H. Expression and significance of TLR4 and HIF-1alpha in pancreatic ductal adenocarcinoma. World J Gastroenterol. 2010;16:2881-8 pubmed
    ..TLR4, NF-kappaB p65 and HIF-1alpha are overexpressed in pancreatic adenocarcinoma, TLR4 may be partly involved in up-regulating HIF-1alpha, and both synergestically promote development of pancreatic adenocarcinoma. ..
  14. Lee S, Lee Y, Song C, Ahn Y, Han H. Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways. Am J Physiol Cell Physiol. 2010;298:C847-56 pubmed publisher
    ..The results indicate that hypoxia increases migration of hMSCs via VEGF-mediated FAK phospholylation and involves the cooperative activity of the ROS, MAPK, eNOS and HIF-1alpha pathways. ..
  15. Dong F, Khalil M, Kiedrowski M, O Connor C, Petrovic E, Zhou X, et al. Critical role for leukocyte hypoxia inducible factor-1alpha expression in post-myocardial infarction left ventricular remodeling. Circ Res. 2010;106:601-10 pubmed publisher
    ..These results demonstrate that WBC infiltration into the newly injured myocardium plays a significant role in left ventricular remodeling, but not infarct size. ..
  16. Melchionna R, Romani M, Ambrosino V, D Arcangelo D, Cencioni C, Porcelli D, et al. Role of HIF-1alpha in proton-mediated CXCR4 down-regulation in endothelial cells. Cardiovasc Res. 2010;86:293-301 pubmed publisher
  17. Zhu P, Ning Y, Yao L, Chen M, Xu C. The proliferation, apoptosis, invasion of endothelial-like epithelial ovarian cancer cells induced by hypoxia. J Exp Clin Cancer Res. 2010;29:124 pubmed publisher
    ..HIF-1? took an important role in the behavioral changes of SKOV-3 and ES-2 cells by hypoxia. At the same time, other mechanisms were also involved in this process. ..
  18. Wei L, Lu J, Feng L, Long D, Shan J, Li S, et al. HIF-1alpha accumulation upregulates MICA and MICB expression on human cardiomyocytes and enhances NK cell cytotoxicity during hypoxia-reoxygenation. Life Sci. 2010;87:111-9 pubmed publisher
    ..These findings suggest that proper control of HIF-1alpha expression via CsA dose may be a potential therapeutic approach for avoiding MIC expression, and improving the function and long-term survival of heart allografts. ..
  19. Mattauch S, Sachs M, Behrens J. Liprin-?4 is a new hypoxia-inducible target gene required for maintenance of cell-cell contacts. Exp Cell Res. 2010;316:2883-92 pubmed publisher
    ..Our data describe for the first time liprin-?4 as a hypoxia-induced gene potentially involved in cell-cell adhesion. ..
  20. Flamant L, Notte A, Ninane N, Raes M, Michiels C. Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia. Mol Cancer. 2010;9:191 pubmed publisher
  21. Dong Z, Yao D, Li S, Li Y, Tai B, Qiu L, et al. [Expression characteristics of hypoxia inducible factor-1a and its clinical values in hepatocellular carcinoma]. Zhonghua Gan Zang Bing Za Zhi. 2010;18:506-10 pubmed publisher
    ..No correlation was found between HIF-1alpha and tumor numbers or positive-HBsAg. HIF-1alpha expression is associated with occurrence and development of HCC, and is perhaps a target molecule for HCC therapy. ..
  22. Corzo C, Condamine T, Lu L, Cotter M, Youn J, Cheng P, et al. HIF-1? regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207:2439-53 pubmed publisher
  23. Sun X, Vale M, Jiang X, Gupta R, Krissansen G. Antisense HIF-1alpha prevents acquired tumor resistance to angiostatin gene therapy. Cancer Gene Ther. 2010;17:532-40 pubmed publisher
    ..The data indicate that blocking hypoxia-inducible pathways by antisense HIF-1alpha can circumvent hypoxia-induced drug resistance and thereby augment the efficacy of anti-angiogenic therapies. ..
  24. Wan X, Fan X, Chen M, Xiang J, Huang P, Guo L, et al. Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor prognosis of nasopharyngeal carcinoma. Autophagy. 2010;6:395-404 pubmed
    ..HI F-1alpha-associated Beclin 1 high expression might facilitate NPC cells surviving from chemoradiotherapy, suggesting a novel therapeutic molecular target for NPC. ..
  25. Xu L, Nilsson M, Saintigny P, Cascone T, Herynk M, Du Z, et al. Epidermal growth factor receptor regulates MET levels and invasiveness through hypoxia-inducible factor-1alpha in non-small cell lung cancer cells. Oncogene. 2010;29:2616-27 pubmed publisher
    ..These findings establish that, absent MET amplification, EGFR signaling can regulate MET levels through HIF-1alpha and that MET is a key downstream mediator of EGFR-induced invasiveness in EGFR-dependent NSCLC cells. ..
  26. Nilsson M, Zage P, Zeng L, Xu L, Cascone T, Wu H, et al. Multiple receptor tyrosine kinases regulate HIF-1alpha and HIF-2alpha in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors. Oncogene. 2010;29:2938-49 pubmed publisher
  27. Tolnay A, Baskin C, Tumpey T, Sabourin P, Sabourin C, Long J, et al. Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus. Arch Virol. 2010;155:905-14 pubmed publisher
    ..Extrapulmonary pathology may thus contribute to the morbidities induced by H5N1 viruses. ..
  28. Zhang Y, Yang Z, Zhang H, Wang C, Liu M, Guo X, et al. Effect of negative pressure on human bone marrow mesenchymal stem cells in vitro. Connect Tissue Res. 2010;51:14-21 pubmed publisher
    ..In conclusion, low-intensity intermittent negative pressure can inhibit the proliferation of human MSCs, induce differentiation to bone cells, promote the OPG mRNA expression, and reduce OPGL mRNA expression. ..
  29. 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...
  30. Chu D, Li V, Yu R. Leptin: clue to poor appetite in oxygen-starved fish. Mol Cell Endocrinol. 2010;319:143-6 pubmed publisher
    ..This is the first report to show that leptin gene expression in fish is regulated by hypoxia possibly via the involvement of HIF-1. ..
  31. Jiang J, Wang Z, Jiang L, Bao Y, Cheng Y. [Mechanism of anti-tumor effect of HIF-1alpha silencing on cervical cancer in nude mice]. Zhonghua Zhong Liu Za Zhi. 2009;31:820-5 pubmed
  32. Eckert A, Schutze A, Lautner M, Taubert H, Schubert J, Bilkenroth U. HIF-1alpha is a prognostic marker in oral squamous cell carcinomas. Int J Biol Markers. 2010;25:87-92 pubmed
    ..Immunohistochemical detection of HIF-1alpha appears to be useful in the diagnosis of OSCC and to provide prognostic information in addition to TNM stage and histological grade...
  33. Shimoyamada H, Yazawa T, Sato H, Okudela K, Ishii J, Sakaeda M, et al. Early growth response-1 induces and enhances vascular endothelial growth factor-A expression in lung cancer cells. Am J Pathol. 2010;177:70-83 pubmed publisher
    ..These findings suggest that EGR-1 plays important roles on VEGF-A expression in lung cancer cells, and epigenetic silencing of transactivator(s) associated with NAB-2 expression might also contribute to upregulate VEGF-A expression. ..
  34. Minematsu T, Nakagami G, Sari Y, Akase T, Sugama J, Nagase T, et al. Candidate biomarkers for deep tissue damage from molecular biological and biochemical aspects. J Tissue Viability. 2010;19:77-83 pubmed publisher
    ..Our results using PU model rats suggested that exudate CPK could be a more sensitive biomarker than serum CPK for deep muscle tissue injury, and could be applicable for clinical diagnosis of DTI. ..
  35. Kim S, Choi Y, Joung S, Lee B, Jung Y, Lee J. Hypoxic stress up-regulates the expression of Toll-like receptor 4 in macrophages via hypoxia-inducible factor. Immunology. 2010;129:516-24 pubmed publisher
  36. Rigopoulos D, Tsiambas E, Lazaris A, Kavantzas N, Papazachariou I, Kravvaritis C, et al. Deregulation of EGFR/VEGF/HIF-1a signaling pathway in colon adenocarcinoma based on tissue microarrays analysis. J BUON. 2010;15:107-15 pubmed
    ..Furthermore, EGFR protein overexpression does not predict a specific gene deregulation mechanism. ..
  37. Doedens A, Stockmann C, Rubinstein M, Liao D, Zhang N, DeNardo D, et al. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 2010;70:7465-75 pubmed publisher
    ..Our findings link the innate immune hypoxic response to tumor progression through induction of T-cell suppression in the tumor microenvironment. ..
  38. Daskalow K, Rohwer N, Raskopf E, Dupuy E, Kühl A, Loddenkemper C, et al. Role of hypoxia-inducible transcription factor 1alpha for progression and chemosensitivity of murine hepatocellular carcinoma. J Mol Med (Berl). 2010;88:817-27 pubmed publisher
    ..However, our data point toward a significant function of HIF-1alpha in determining chemosensitivity of HCC and therefore warrant validation of HIF-1alpha-inhibitors as adjuvant therapeutic agents in clinical studies of human HCC. ..
  39. Graves E, Maity A, Le Q. The tumor microenvironment in non-small-cell lung cancer. Semin Radiat Oncol. 2010;20:156-63 pubmed publisher
    ..Presently, there are several promising modalities to image hypoxia and the tumor vasculature; these include dynamic perfusion imaging and positron emission tomography scanning with radiolabled nitroimidazoles. ..
  40. Huang C, Yang W, Chang S, Tai S, Tzeng C, Kao J, et al. Regulation of membrane-type 4 matrix metalloproteinase by SLUG contributes to hypoxia-mediated metastasis. Neoplasia. 2009;11:1371-82 pubmed
    ..These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis. ..
  41. Rosmorduc O, Housset C. Hypoxia: a link between fibrogenesis, angiogenesis, and carcinogenesis in liver disease. Semin Liver Dis. 2010;30:258-70 pubmed publisher
  42. Oh J, Moon E. Actin-sequestering protein, thymosin beta-4, induces paclitaxel resistance through ROS/HIF-1alpha stabilization in HeLa human cervical tumor cells. Life Sci. 2010;87:286-93 pubmed publisher
    ..It suggests that soluble TB4 could be a novel endogenous regulator to control intracellular ROS production in tumor cells. ..
  43. Kojima H, Kobayashi A, Sakurai D, Kanno Y, Hase H, Takahashi R, et al. Differentiation stage-specific requirement in hypoxia-inducible factor-1alpha-regulated glycolytic pathway during murine B cell development in bone marrow. J Immunol. 2010;184:154-63 pubmed publisher
    ..Taken together, these findings indicate that glucose dependency differs at different B cell developmental stages and that HIF-1alpha plays an important role in B cell development. ..
  44. Shen R, Jiang X, Pu J, Zou S. HIF-1alpha and -2alpha genes in a hypoxia-sensitive teleost species Megalobrama amblycephala: cDNA cloning, expression and different responses to hypoxia. Comp Biochem Physiol B Biochem Mol Biol. 2010;157:273-80 pubmed publisher
    ..These results suggest that the Wuchang bream HIF-1alpha and -2alpha would be involved in different physiological functions under normoxia and hypoxia situations. ..
  45. Bian C, Shi Z, Meng Q, Jiang Y, Liu L, Jiang B. P70S6K 1 regulation of angiogenesis through VEGF and HIF-1alpha expression. Biochem Biophys Res Commun. 2010;398:395-9 pubmed publisher
    ..Our results suggest that p70S6K1 is required for tumor growth and angiogenesis through HIF-1alpha and VEGF expression, providing a molecular mechanism of human ovarian cancer mediated by p70S6K1 signaling. ..
  46. Yun Y, Li S, Cho Y, Park J, Chun Y. Survivin mediates prostate cell protection by HIF-1alpha against zinc toxicity. Prostate. 2010;70:1179-88 pubmed publisher
    ..Accordingly, the HIF-1alpha-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia. ..
  47. Bawa Khalfe T, Cheng J, Lin S, Ittmann M, Yeh E. SENP1 induces prostatic intraepithelial neoplasia through multiple mechanisms. J Biol Chem. 2010;285:25859-66 pubmed publisher
    ..These results demonstrate that deSUMOylation plays a critical role in prostate pathogenesis through induction of HIF1alpha-dependent angiogenesis and enhanced cell proliferation. ..
  48. Chen C, Ostrowski R, Zhou C, Tang J, Zhang J. Suppression of hypoxia-inducible factor-1alpha and its downstream genes reduces acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of cerebral ischemia. J Neurosci Res. 2010;88:2046-55 pubmed publisher
    ..In conclusion, the inhibition of HIF-1alpha and its downstream genes attenuates hemorrhagic conversion of cerebral infarction and ameliorates neurological deficits after focal cerebral ischemia. ..
  49. Dehne N, Hintereder G, Brüne B. High glucose concentrations attenuate hypoxia-inducible factor-1alpha expression and signaling in non-tumor cells. Exp Cell Res. 2010;316:1179-89 pubmed publisher
  50. Chan D, Giaccia A. PHD2 in tumour angiogenesis. Br J Cancer. 2010;103:1-5 pubmed publisher
    ..This review summarises our current understanding of PHD2 and tumour angiogenesis, focusing on the influences of PHD2 on vascular normalisation and neovascularisation. ..
  51. Tan T, Marin Garcia J, Damle S, Weiss H. Hypoxia-inducible factor-1 improves inotropic responses of cardiac myocytes in ageing heart without affecting mitochondrial activity. Exp Physiol. 2010;95:712-22 pubmed publisher
    ..Thus, we found that HIF-1 improved inotropy in older myocytes without requiring mitochondrial activity changes...
  52. Brooks A, Menzies Gow N, Bailey S, Cunningham F, Elliott J. Endotoxin-induced HIF-1alpha stabilisation in equine endothelial cells: synergistic action with hypoxia. Inflamm Res. 2010;59:689-98 pubmed publisher
    ..Exposure of EDVEC to LPS prior to induction of hypoxia up-regulates responses that may enhance LPS-induced tissue damage in the endotoxaemic horse. Inhibitors of p38 MAPK or HIF-1alpha could reduce such unwanted effects. ..
  53. Wang Z, Kang J, Dai B. [Expression and activation of hypoxia inducible factor-1alpha and iNOS in the brain of rats with chronic intermittent hypoxia]. Zhonghua Jie He He Hu Xi Za Zhi. 2009;32:739-43 pubmed
    ..HIF-1 may be a key factor in up-regulation of the transcription of iNOS under chronic intermittent hypoxia. HIF-1 promotes the transcription of iNOS though enhanced binding activity. ..