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Gene Review

HMOX2  -  heme oxygenase (decycling) 2

Homo sapiens

Synonyms: HO-2, HO2, Heme oxygenase 2
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Disease relevance of HMOX2


High impact information on HMOX2

  • 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) [6].
  • On the other hand, massive neuronal firing during a stroke presumably activates HO2, leading to neuroprotective actions of bilirubin [7].
  • The reduced expression of HO-2 on endothelial cells in PE and FGR may be responsible for reduced placental blood flow in these conditions [8].
  • However, immunohistochemical analysis showed a reduction in HO-2 expression in endothelial cells in both abnormal groups (PE P<0.01; FGR P<0.0005 vs. control group) but no differences in villous trophoblast staining [8].
  • Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO-2 in preeclampsia and fetal growth restriction [8].

Chemical compound and disease context of HMOX2


Biological context of HMOX2


Anatomical context of HMOX2


Associations of HMOX2 with chemical compounds

  • The calcium mobilizing agents ionomycin and glutamate stimulate endogenous HO2 activity in primary cortical cultures, establishing in vivo relevance [17].
  • However, there was no correlation between HO-2 protein content and HO enzymatic activity in HTR-8/SVneo trophoblast cells preexposed to 0.5% O2 and low glucose concentration for 24 h [18].
  • A type II change (red shift) of the Soret band (405 nm --> 413-419 nm) was observed when wild-type HO-2 was treated with sodium nitroprusside (SNP), S-nitroglutathione (GSNO), S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1); the NO scavenger, hydroxocobalamin (HCB) prevented the shift [19].
  • NO donors significantly inhibited HO-2 activity, with SNP being the most potent inhibitor (> 40%) [19].
  • Only SIN-1, which produces peroxynitrite by generating both NO and superoxide anion, decreased the Soret region absorption and the pyridine hemochromogen spectrum of HO-2; superoxide dismutase (SOD) blocked the decrease [19].
  • We propose that the HRMs in HO-2 constitute a thiol/disulfide redox switch that regulates the myriad physiological functions of HO-2, including its involvement in the hypoxic response in the carotid body, which involves interactions with a Ca(2+)-activated potassium channel [20].

Regulatory relationships of HMOX2

  • Transient transfection assays in HeLa cells revealed that the 4.5-kb human HO-1 gene promoter was activated with selective knockdown of HO-2 in a sequence-dependent manner [2].
  • HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD [21].

Other interactions of HMOX2


Analytical, diagnostic and therapeutic context of HMOX2

  • Using in situ hybridization histochemistry, we noted a pronounced increase in signal for HO-2 mRNA in the brain of 14-day-old rats postnatally treated with corticosterone (5 microg/g, 4 x, starting 24-36 h after birth) [15].
  • The current study was undertaken to investigate the role of HO-2 in the regulation of the acute inflammatory and reparative response by using HO-2-null mice and well-established animal models of epithelial injury and antigen-induced peritonitis [3].
  • Total RNA from renal samples was reverse transcribed and amplified simultaneously by PCR using specific primers for HO-1 and HO-2 [27].
  • Additional confocal microscopy studies using c-Kit staining demonstrated the localization of HO-2 IR and nNOS IR in interstitial cells of Cajal (ICC) of the anorectum [28].
  • HO enzymatic activity was measured under optimized conditions by gas chromatography using CO formation as an index of activity, and HO-1 and HO-2 protein content were determined by Western immunoblot analysis [29].


  1. Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors. Takahashi, K., Hara, E., Suzuki, H., Sasano, H., Shibahara, S. J. Neurochem. (1996) [Pubmed]
  2. Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell lines. Ding, Y., Zhang, Y.Z., Furuyama, K., Ogawa, K., Igarashi, K., Shibahara, S. FEBS J. (2006) [Pubmed]
  3. Heme oxygenase-2 is a critical determinant for execution of an acute inflammatory and reparative response. Seta, F., Bellner, L., Rezzani, R., Regan, R.F., Dunn, M.W., Abraham, N.G., Gronert, K., Laniado-Schwartzman, M. Am. J. Pathol. (2006) [Pubmed]
  4. Localization of heme oxygenase-2 immunoreactivity to parasympathetic ganglia of human and guinea-pig airways. Canning, B.J., Fischer, A. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  5. Characterization of a cDNA-encoding rabbit brain heme oxygenase-2 and identification of a conserved domain among mammalian heme oxygenase isozymes: possible heme-binding site? Rotenberg, M.O., Maines, M.D. Arch. Biochem. Biophys. (1991) [Pubmed]
  6. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Ryter, S.W., Alam, J., Choi, A.M. Physiol. Rev. (2006) [Pubmed]
  7. Neural roles for heme oxygenase: contrasts to nitric oxide synthase. Barañano, D.E., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO-2 in preeclampsia and fetal growth restriction. Barber, A., Robson, S.C., Myatt, L., Bulmer, J.N., Lyall, F. FASEB J. (2001) [Pubmed]
  9. Expression of heme oxygenase-1 (HSP32) in human prostate: normal, hyperplastic, and tumor tissue distribution. Maines, M.D., Abrahamsson, P.A. Urology (1996) [Pubmed]
  10. Heme oxygenase (HO) isoforms in experimental C6 glioma: an immunocytochemical study. Lo, S., Bell, H.S., Yamaguchi, S., Wharton, S.B., Whittle, I.R. British journal of neurosurgery. (2001) [Pubmed]
  11. Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells. Rieder, C.R., Williams, A.C., Ramsden, D.B. Braz. J. Med. Biol. Res. (2004) [Pubmed]
  12. Differential expression of heme oxygenase-1 in cultured cortical neurons and astrocytes determined by the aid of a new heme oxygenase antibody. Response to oxidative stress. Dwyer, B.E., Nishimura, R.N., Lu, S.Y. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  13. Expression and localization of heme oxygenase in human placental villi. Yoshiki, N., Kubota, T., Aso, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  14. Effects of hypoxia on heme oxygenase expression in human chorionic villi explants and immortalized trophoblast cells. Appleton, S.D., Marks, G.S., Nakatsu, K., Brien, J.F., Smith, G.N., Graham, C.H., Lash, G.E. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  15. Regulation of heme oxygenase-2 by glucocorticoids in neonatal rat brain: characterization of a functional glucocorticoid response element. Raju, V.S., McCoubrey, W.K., Maines, M.D. Biochim. Biophys. Acta (1997) [Pubmed]
  16. Rickettsia rickettsii infection of cultured human endothelial cells induces heme oxygenase 1 expression. Rydkina, E., Sahni, A., Silverman, D.J., Sahni, S.K. Infect. Immun. (2002) [Pubmed]
  17. Heme oxygenase-2 is activated by calcium-calmodulin. Boehning, D., Sedaghat, L., Sedlak, T.W., Snyder, S.H. J. Biol. Chem. (2004) [Pubmed]
  18. 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]
  19. Interaction of heme oxygenase-2 with nitric oxide donors. Is the oxygenase an intracellular 'sink' for NO? Ding, Y., McCoubrey, W.K., Maines, M.D. Eur. J. Biochem. (1999) [Pubmed]
  20. Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a thiol/disulfide redox switch regulating heme binding. Yi, L., Ragsdale, S.W. J. Biol. Chem. (2007) [Pubmed]
  21. Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients. Maestrelli, P., Páska, C., Saetta, M., Turato, G., Nowicki, Y., Monti, S., Formichi, B., Miniati, M., Fabbri, L.M. Eur. Respir. J. (2003) [Pubmed]
  22. Induction of placental heme oxygenase-1 is protective against TNFalpha-induced cytotoxicity and promotes vessel relaxation. Ahmed, A., Rahman, M., Zhang, X., Acevedo, C.H., Nijjar, S., Rushton, I., Bussolati, B., St John, J. Mol. Med. (2000) [Pubmed]
  23. Increased expression and activity of heme oxygenase-2 in pregnant rat aorta is not involved in attenuated vasopressin-induced contraction. Katoue, M.G., Khan, I., Oriowo, M.A. Naunyn Schmiedebergs Arch. Pharmacol. (2005) [Pubmed]
  24. 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]
  25. Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase. Hedlund, P., Ny, L., Alm, P., Andersson, K.E. J. Urol. (2000) [Pubmed]
  26. Functional proteomics of BK potassium channels: defining the acute oxygen sensor. Kemp, P.J., Williams, S.E., Mason, H.S., Wootton, P., Iles, D.E., Riccardi, D., Peers, C. Novartis Found. Symp. (2006) [Pubmed]
  27. 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]
  28. Heme oxygenase-2 distribution in anorectum: colocalization with neuronal nitric oxide synthase. Battish, R., Cao, G.Y., Lynn, R.B., Chakder, S., Rattan, S. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  29. Heme oxygenase expression in selected regions of term human placenta. McLaughlin, B.E., Lash, G.E., Smith, G.N., Marks, G.S., Nakatsu, K., Graham, C.H., Brien, J.F. Exp. Biol. Med. (Maywood) (2003) [Pubmed]
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