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Gene Review

HMOX1  -  heme oxygenase (decycling) 1

Homo sapiens

Synonyms: HMOX1D, HO, HO-1, HO1, HSP32, ...
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Disease relevance of HMOX1


Psychiatry related information on HMOX1


High impact information on HMOX1

  • The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO) [10].
  • Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications [10].
  • This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress [10].
  • IL-10-mediated protection against LPS-induced septic shock in mice was significantly attenuated by cotreatment with the HO inhibitor, zinc protoporphyrin [11].
  • Here we report that HO-1 directly reduces vasoconstriction and inhibits cell proliferation during vascular injury [12].

Chemical compound and disease context of HMOX1


Biological context of HMOX1

  • We sequenced HMOX1 and found a T(-413)A polymorphism in the promoter region [1].
  • A (GT)(n) dinucleotide repeat in the 5'-flanking region of the human HO-1 gene (alias HMOX1) reduces HO-1 inducibility and shows length polymorphism, which is grouped into three classes: class S (<27 GT), class M (27-32 GT), and class L (>/=33 GT) alleles [18].
  • We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO) [19].
  • Heme oxygenase-1 (HO-1) protects cells from various insults including oxidative stress [20].
  • Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene [20].

Anatomical context of HMOX1


Associations of HMOX1 with chemical compounds


Physical interactions of HMOX1


Enzymatic interactions of HMOX1


Regulatory relationships of HMOX1


Other interactions of HMOX1

  • In controls, approximately 50% of the total HO activity was from HO-1 as judged by the sensitivity to GTS-1, while the rest of activity was from other isozymes such as HO-2 [3].
  • From a comparison of heavy metal responses of several human genes, it was noted that the heme oxygenase-1 (HO-1) gene is quite similar in the spectrum of metal response and induction kinetics to the heat shock protein 70 (HSP70) gene, suggesting a common regulatory mechanism shared by these genes [40].
  • Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C [41].
  • In hBVR-infected cells, levels of HO-1 mRNA and protein were increased [32].
  • Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of cAMP-responsive element-binding protein [42].

Analytical, diagnostic and therapeutic context of HMOX1


  1. A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese. Ono, K., Goto, Y., Takagi, S., Baba, S., Tago, N., Nonogi, H., Iwai, N. Atherosclerosis (2004) [Pubmed]
  2. Mechanism of Action of Sulforaphane: Inhibition of p38 Mitogen-Activated Protein Kinase Isoforms Contributing to the Induction of Antioxidant Response Element-Mediated Heme Oxygenase-1 in Human Hepatoma HepG2 Cells. Keum, Y.S., Yu, S., Chang, P.P., Yuan, X., Kim, J.H., Xu, C., Han, J., Agarwal, A., Kong, A.N. Cancer Res. (2006) [Pubmed]
  3. Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. Makino, N., Suematsu, M., Sugiura, Y., Morikawa, H., Shiomi, S., Goda, N., Sano, T., Nimura, Y., Sugimachi, K., Ishimura, Y. Hepatology (2001) [Pubmed]
  4. Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells. Liu, Z.M., Chen, G.G., Ng, E.K., Leung, W.K., Sung, J.J., Chung, S.C. Oncogene (2004) [Pubmed]
  5. Nitric oxide induces heme oxygenase-1 via mitogen-activated protein kinases ERK and p38. Chen, K., Maines, M.D. Cell. Mol. Biol. (Noisy-le-grand) (2000) [Pubmed]
  6. Increased HO-1 expression and decreased iNOS expression in the hippocampus from adult spontaneously hypertensive rats. Huang, Y., Wu, L., Xu, C., Yang, B., Wang, R. Cell Biochem. Biophys. (2006) [Pubmed]
  7. Regulation of heme oxygenase expression by cyclopentenone prostaglandins. Zhuang, H., Pin, S., Li, X., Doré, S. Exp. Biol. Med. (Maywood) (2003) [Pubmed]
  8. Protection of human vascular smooth muscle cells from H2O2-induced apoptosis through functional codependence between HO-1 and AKT. Brunt, K.R., Fenrich, K.K., Kiani, G., Tse, M.Y., Pang, S.C., Ward, C.A., Melo, L.G. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  9. Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD. Schipper, H.M., Chertkow, H., Mehindate, K., Frankel, D., Melmed, C., Bergman, H. Neurology (2000) [Pubmed]
  10. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Ryter, S.W., Alam, J., Choi, A.M. Physiol. Rev. (2006) [Pubmed]
  11. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Lee, T.S., Chau, L.Y. Nat. Med. (2002) [Pubmed]
  12. Heme oxygenase-1 protects against vascular constriction and proliferation. Duckers, H.J., Boehm, M., True, A.L., Yet, S.F., San, H., Park, J.L., Clinton Webb, R., Lee, M.E., Nabel, G.J., Nabel, E.G. Nat. Med. (2001) [Pubmed]
  13. Tin-protoporphyrin-mediated disruption in vivo of heme oxygenase-2 protein integrity and activity in rat brain. Mark, J.A., Maines, M.D. Pediatr. Res. (1992) [Pubmed]
  14. Heme oxygenase-1 inhibits apoptosis in Caco-2 cells via activation of Akt pathway. Busserolles, J., Megías, J., Terencio, M.C., Alcaraz, M.J. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  15. Overexpression of the heme oxygenase gene in renal cell carcinoma. Goodman, A.I., Choudhury, M., da Silva, J.L., Schwartzman, M.L., Abraham, N.G. Proc. Soc. Exp. Biol. Med. (1997) [Pubmed]
  16. Effect of glucose and oxygen deprivation on heme oxygenase expression in human chorionic villi explants and immortalized trophoblast cells. Appleton, S.D., Lash, G.E., Marks, G.S., Nakatsu, K., Brien, J.F., Smith, G.N., Graham, C.H. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  17. Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6. Chen, Y.C., Chow, J.M., Lin, C.W., Wu, C.Y., Shen, S.C. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  18. Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism. Kikuchi, A., Yamaya, M., Suzuki, S., Yasuda, H., Kubo, H., Nakayama, K., Handa, M., Sasaki, T., Shibahara, S., Sekizawa, K., Sasaki, H. Hum. Genet. (2005) [Pubmed]
  19. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. Brouard, S., Otterbein, L.E., Anrather, J., Tobiasch, E., Bach, F.H., Choi, A.M., Soares, M.P. J. Exp. Med. (2000) [Pubmed]
  20. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. Sun, J., Hoshino, H., Takaku, K., Nakajima, O., Muto, A., Suzuki, H., Tashiro, S., Takahashi, S., Shibahara, S., Alam, J., Taketo, M.M., Yamamoto, M., Igarashi, K. EMBO J. (2002) [Pubmed]
  21. The heme-heme oxygenase system: a molecular switch in wound healing. Wagener, F.A., van Beurden, H.E., von den Hoff, J.W., Adema, G.J., Figdor, C.G. Blood (2003) [Pubmed]
  22. Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Doré, S., Takahashi, M., Ferris, C.D., Zakhary, R., Hester, L.D., Guastella, D., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  23. Human biliverdin reductase is autophosphorylated, and phosphorylation is required for bilirubin formation. Salim, M., Brown-Kipphut, B.A., Maines, M.D. J. Biol. Chem. (2001) [Pubmed]
  24. Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene. Suzuki, H., Tashiro, S., Sun, J., Doi, H., Satomi, S., Igarashi, K. J. Biol. Chem. (2003) [Pubmed]
  25. Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells. Kondo, R., Gleixner, K.V., Mayerhofer, M., Vales, A., Gruze, A., Samorapoompichit, P., Greish, K., Krauth, M.T., Aichberger, K.J., Pickl, W.F., Esterbauer, H., Sillaber, C., Maeda, H., Valent, P. Blood (2007) [Pubmed]
  26. Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes. Vareille, M., Rannou, F., Thélier, N., Glasser, A.L., de Sablet, T., Martin, C., Gobert, A.P. J. Immunol. (2008) [Pubmed]
  27. Human biliverdin reductase is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress. Ahmad, Z., Salim, M., Maines, M.D. J. Biol. Chem. (2002) [Pubmed]
  28. Vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-beta and reactive oxygen species generation in human retinal pigment epithelial cells. Hartung, R., Parapuram, S.K., Ganti, R., Hunt, D.M., Chalam, K.V., Hunt, R.C. Mol. Vis. (2007) [Pubmed]
  29. Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells. Ogborne, R.M., Rushworth, S.A., O'Connell, M.A. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  30. Heme oxygenase is a positive acute-phase reactant in human Hep3B hepatoma cells. Mitani, K., Fujita, H., Kappas, A., Sassa, S. Blood (1992) [Pubmed]
  31. Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells. Li, M.H., Cha, Y.N., Surh, Y.J. Free Radic. Biol. Med. (2006) [Pubmed]
  32. Biliverdin reductase, a novel regulator for induction of activating transcription factor-2 and heme oxygenase-1. Kravets, A., Hu, Z., Miralem, T., Torno, M.D., Maines, M.D. J. Biol. Chem. (2004) [Pubmed]
  33. The binding sites on human heme oxygenase-1 for cytochrome p450 reductase and biliverdin reductase. Wang, J., de Montellano, P.R. J. Biol. Chem. (2003) [Pubmed]
  34. Crystallization of recombinant human heme oxygenase-1. Schuller, D.J., Wilks, A., Ortiz de Montellano, P., Poulos, T.L. Protein Sci. (1998) [Pubmed]
  35. Effect of heme and heme oxygenase-1 on vascular endothelial growth factor synthesis and angiogenic potency of human keratinocytes. Jazwa, A., Loboda, A., Golda, S., Cisowski, J., Szelag, M., Zagorska, A., Sroczynska, P., Drukala, J., Jozkowicz, A., Dulak, J. Free Radic. Biol. Med. (2006) [Pubmed]
  36. A molecular cascade showing nitric oxide-heme oxygenase-1-vascular endothelial growth factor-interleukin-8 sequence in human endothelial cells. Pae, H.O., Oh, G.S., Choi, B.M., Kim, Y.M., Chung, H.T. Endocrinology (2005) [Pubmed]
  37. Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression. Wagener, F.A., da Silva, J.L., Farley, T., de Witte, T., Kappas, A., Abraham, N.G. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  38. Induction of heme oxygenase-1 inhibits monocyte chemoattractant protein-1 mRNA expression in U937 cells. Shokawa, T., Yoshizumi, M., Yamamoto, H., Omura, S., Toyofuku, M., Shimizu, Y., Imazu, M., Kohno, N. J. Pharmacol. Sci. (2006) [Pubmed]
  39. Targeting endothelial cells with heme oxygenase-1 gene using VE-cadherin promoter attenuates hyperglycemia-mediated cell injury and apoptosis. Asija, A., Peterson, S.J., Stec, D.E., Abraham, N.G. Antioxid. Redox Signal. (2007) [Pubmed]
  40. Cadmium-responsive Element of the Human Heme Oxygenase-1 Gene Mediates Heat Shock Factor 1-dependent Transcriptional Activation. Koizumi, S., Gong, P., Suzuki, K., Murata, M. J. Biol. Chem. (2007) [Pubmed]
  41. Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C. Rushworth, S.A., Chen, X.L., Mackman, N., Ogborne, R.M., O'Connell, M.A. J. Immunol. (2005) [Pubmed]
  42. Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of cAMP-responsive element-binding protein. Krönke, G., Bochkov, V.N., Huber, J., Gruber, F., Blüml, S., Fürnkranz, A., Kadl, A., Binder, B.R., Leitinger, N. J. Biol. Chem. (2003) [Pubmed]
  43. Small interference RNA-mediated gene silencing of human biliverdin reductase, but not that of heme oxygenase-1, attenuates arsenite-mediated induction of the oxygenase and increases apoptosis in 293A kidney cells. Miralem, T., Hu, Z., Torno, M.D., Lelli, K.M., Maines, M.D. J. Biol. Chem. (2005) [Pubmed]
  44. Heme oxygenase-1 gene activation by the NAD(P)H oxidase inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride via a protein kinase B, p38-dependent signaling pathway in monocytes. Wijayanti, N., Kietzmann, T., Immenschuh, S. J. Biol. Chem. (2005) [Pubmed]
  45. Expression of the heme oxygenase-carbon monoxide signalling system in human placenta. McLean, M., Bowman, M., Clifton, V., Smith, R., Grossman, A.B. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  46. Heme oxygenase and the cardiovascular-renal system. Abraham, N.G., Kappas, A. Free Radic. Biol. Med. (2005) [Pubmed]
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