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Gene Review

Hmox2  -  heme oxygenase (decycling) 2

Rattus norvegicus

Synonyms: HO-2, Heme oxygenase 2
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Disease relevance of Hmox2

  • In contrast, the two HO-2 homologous transcripts (1.3 and 1.9 kilobases) did not respond to heat shock; neither the ratio nor the level of the two messages differed from that of the control when measured either at 1, 6, or 24 h after hyperthermia [1].
  • In contrast to HO-2, a significant increase in HO-1 on the whole organ level was noted by hemorrhagic hypotension, GSH depletion, and cobalt chloride injection [2].
  • Presently a rat HO-2 cDNA (Rotenberg, M.O., and Maines, M. D. (1990) J. Biol. Chem. 265, 7501-7506) was used to generate a construct with a neutral hydrophobicity profile at its COOH terminus for expression of nearly full-length HO-2 protein in Escherichia coli [3].
  • Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered aortic reactivity after hypoxia in rats [4].
  • We show expression of HO-1 and HO-2 at both the transcription and protein levels under normal conditions in the heart and descending aorta, and demonstrate the sensitivity of only the HO-1 isozyme to heat stress in these tissues [5].

Psychiatry related information on Hmox2

  • The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have different functions [6]?
  • In light of the recently reported inhibitory interaction between HO-2/CO and amyloid-beta, a marker of Alzheimer's disease (AD), we speculate that HO-2/CO signaling may be a defective component of cholinergic neurotransmission in the pathophysiology of AD, whose manifestations include disintegration of circadian timing [7].

High impact information on Hmox2


Chemical compound and disease context of Hmox2


Biological context of Hmox2


Anatomical context of Hmox2


Associations of Hmox2 with chemical compounds

  • A multistep protocol developed for isolation of HO-2 resulted in a homogeneous protein with a specific activity up to 6,500 nmol of bilirubin/mg/h. Based on SDS-polyacrylamide gel electrophoresis and Western blot analyses, the protein had an apparent molecular mass of approximately 34 kDa [3].
  • Major differences, however, were noted in the amino acid composition of the two forms including the presence of 3 cysteine/cystine residues in HO-2 only [16].
  • The neurotoxic heme is usually detoxified by the constitutive heme oxygenase-2 (HO-2) and its inducible isoform HO-1(heat shock protein 32) resulting in the formation of biliverdin which becomes reduced to bilirubin, carbon monoxide (CO), and iron [20].
  • In adult rat testis, corticosterone treatment, however, was not an effective regulator of HO-2 transcript populations or levels [21].
  • HO-2 is a constitutive isoform of heme oxygenase (HO), a microsomal enzyme that catalyzes the cleavage of the heme ring to form ferrous iron, carbon monoxide, and biliverdin [22].

Regulatory relationships of Hmox2

  • The transcripts for HO-1 in the renal outer medulla and inner medulla were 2.5 and 3.7 times that expressed in the renal cortex and those for HO-2 in the outer medulla and inner medulla were 1.3 and 1.6 times that expressed in the renal cortex, respectively [23].

Other interactions of Hmox2

  • Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein [1].
  • Interaction of Fe-protoporphyrin IX and heme analogues with purified recombinant heme oxygenase-2, the constitutive isozyme of the brain and testes [3].
  • Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats [24].
  • In the corpus cavernosum of SHR, expression of the HO-2 and nNOS genes was similar, and NOx levels after EFS were similar to those of WKY. cGMP levels after EFS and the relaxation evoked by the NO donor was lower in SHR than WKY [25].
  • TGF-beta1 also decreased HO-1 but not HO-2 protein expression in these cells [26].

Analytical, diagnostic and therapeutic context of Hmox2

  • HO-2 immunohistochemistry showed that the number of HO-2-positive neurons in most perilesional regions remained constant [20].
  • Northern blot analysis was used to demonstrate the presence of five transcripts for HO-2 in rat testis mRNA; they range from approximately 1.3 to approximately 2.1 kg in length with a predominant 1.45-kb message; three of the transcripts, approximately 1.45 kb, approximately 1.7 kb, and approximately 2.1 kg, are unique to testis [17].
  • Frozen tissues were subjected to HO-1 and HO-2 mRNA expression by real-time RT-PCR and HO activity determination [27].
  • The ratio of the two HO-2 homologous transcripts (approximately 1.9 and 1.3 Kb) present in the atrium, ventricles and descending aorta and their levels were not altered by hyperthermia (42 degrees C, 20 min) when measured 1 or 6 hr after treatment [5].
  • Antiserum to the liver HO-1 did not recognize the testicular HO-2 when examined by double immunodiffusion or by Western immunoblotting [28].


  1. Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein. Ewing, J.F., Maines, M.D. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  2. Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver. Bauer, I., Wanner, G.A., Rensing, H., Alte, C., Miescher, E.A., Wolf, B., Pannen, B.H., Clemens, M.G., Bauer, M. Hepatology (1998) [Pubmed]
  3. Interaction of Fe-protoporphyrin IX and heme analogues with purified recombinant heme oxygenase-2, the constitutive isozyme of the brain and testes. Rublevskaya, I., Maines, M.D. J. Biol. Chem. (1994) [Pubmed]
  4. Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered aortic reactivity after hypoxia in rats. Govindaraju, V., Teoh, H., Hamid, Q., Cernacek, P., Ward, M.E. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  5. Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3':5'-guanosine monophosphate. Ewing, J.F., Raju, V.S., Maines, M.D. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  6. The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have different functions? Maines, M.D., Panahian, N. Adv. Exp. Med. Biol. (2001) [Pubmed]
  7. Carbon monoxide and nitric oxide: interacting messengers in muscarinic signaling to the brain's circadian clock. Artinian, L.R., Ding, J.M., Gillette, M.U. Exp. Neurol. (2001) [Pubmed]
  8. Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors. Kaide, J.I., Zhang, F., Wei, Y., Jiang, H., Yu, C., Wang, W.H., Balazy, M., Abraham, N.G., Nasjletti, A. J. Clin. Invest. (2001) [Pubmed]
  9. Carbon monoxide stimulates the apical 70-pS K+ channel of the rat thick ascending limb. Liu, H., Mount, D.B., Nasjletti, A., Wang, W. J. Clin. Invest. (1999) [Pubmed]
  10. Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta. Ishizaka, N., de León, H., Laursen, J.B., Fukui, T., Wilcox, J.N., De Keulenaer, G., Griendling, K.K., Alexander, R.W. Circulation (1997) [Pubmed]
  11. Carbon monoxide: a role in carotid body chemoreception. Prabhakar, N.R., Dinerman, J.L., Agani, F.H., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  12. Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis. McCoubrey, W.K., Huang, T.J., Maines, M.D. J. Biol. Chem. (1997) [Pubmed]
  13. Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology. Bidmon, H.J., Emde, B., Kowalski, T., Schmitt, M., Mayer, B., Kato, K., Asayama, K., Witte, O.W., Zilles, K. J. Chem. Neuroanat. (2001) [Pubmed]
  14. Depletion of endogenous serotonin synthesis with p-CPA attenuates upregulation of constitutive isoform of heme oxygenase-2 expression, edema formation and cell injury following a focal trauma to the rat spinal cord. Sharma, H.S., Westman, J. Acta Neurochir. Suppl. (2003) [Pubmed]
  15. Antioxidant compounds EGB-761 and BN-52021 attenuate brain edema formation and hemeoxygenase expression following hyperthermic brain injury in the rat. Sharma, H.S., Drieu, K., Westman, J. Acta Neurochir. Suppl. (2003) [Pubmed]
  16. Evidence suggesting that the two forms of heme oxygenase are products of different genes. Cruse, I., Maines, M.D. J. Biol. Chem. (1988) [Pubmed]
  17. Multiple transcripts encoding heme oxygenase-2 in rat testis: developmental and cell-specific regulation of transcripts and protein. McCoubrey, W.K., Eke, B., Maines, M.D. Biol. Reprod. (1995) [Pubmed]
  18. Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Hayashi, S., Omata, Y., Sakamoto, H., Higashimoto, Y., Hara, T., Sagara, Y., Noguchi, M. Gene (2004) [Pubmed]
  19. Localization of heme oxygenase in rat retina: effect of light adaptation. Nishimura, R.N., Dwyer, B.E., Lu, S.Y. Neurosci. Lett. (1996) [Pubmed]
  20. Heme oxygenase-1 (HSP-32) and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis. Bidmon, H.J., Emde, B., Oermann, E., Kubitz, R., Witte, O.W., Zilles, K. Exp. Neurol. (2001) [Pubmed]
  21. Developmentally regulated expression of two transcripts for heme oxygenase-2 with a first exon unique to rat testis: control by corticosterone of the oxygenase protein expression. Liu, N., Wang, X., McCoubrey, W.K., Maines, M.D. Gene (2000) [Pubmed]
  22. Quetiapine and venlafaxine synergically regulate heme oxygenase-2 protein expression in the hippocampus of stressed rats. Chen, Z., Xu, H., Haimano, S., Li, X., Li, X.M. Neurosci. Lett. (2005) [Pubmed]
  23. Expression and actions of heme oxygenase in the renal medulla of rats. Zou, A.P., Billington, H., Su, N., Cowley, A.W. Hypertension (2000) [Pubmed]
  24. Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats. Lee, Y.M., Cheng, P.Y., Hong, S.F., Chen, S.Y., Lam, K.K., Sheu, J.R., Yen, M.H. Free Radic. Biol. Med. (2005) [Pubmed]
  25. Erectile dysfunction in hypertensive rats results from impairment of the relaxation evoked by neurogenic carbon monoxide and nitric oxide. Ushiyama, M., Morita, T., Kuramochi, T., Yagi, S., Katayama, S. Hypertens. Res. (2004) [Pubmed]
  26. Induction of heme oxygenase-1 during endotoxemia is downregulated by transforming growth factor-beta1. Pellacani, A., Wiesel, P., Sharma, A., Foster, L.C., Huggins, G.S., Yet, S.F., Perrella, M.A. Circ. Res. (1998) [Pubmed]
  27. Heme oxygenase in diabetes-induced oxidative stress in the heart. Farhangkhoee, H., Khan, Z.A., Mukherjee, S., Cukiernik, M., Barbin, Y.P., Karmazyn, M., Chakrabarti, S. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  28. Purification and characterization of the major constitutive form of testicular heme oxygenase. The noninducible isoform. Trakshel, G.M., Kutty, R.K., Maines, M.D. J. Biol. Chem. (1986) [Pubmed]
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