Gene Symbol: Hmox2
Description: heme oxygenase 2
Alias: Ho-2, heme oxygenase 2, heme oxygenase (decycling) 2, heme oxygenase-2 non-reducing isoform
Species: rat
Products:     Hmox2

Top Publications

  1. West A, Oates P. Subcellular location of heme oxygenase 1 and 2 and divalent metal transporter 1 in relation to endocytotic markers during heme iron absorption. J Gastroenterol Hepatol. 2008;23:150-8 pubmed
    ..The lack of translocation of DMT1 with heme dosing suggests another protein may be present to transport iron released from heme. ..
  2. Abrahám S, Hermesz E, Szabo A, Ferencz A, Jancsó Z, Duda E, et al. Effects of Kupffer cell blockade on the hepatic expression of metallothionein and heme oxygenase genes in endotoxemic rats with obstructive jaundice. Life Sci. 2012;90:140-6 pubmed publisher
    ..In response to GdCl?, HO-1 induction was significantly lower in each model. Despite its moderate hepatocellular toxicity, the ameliorated stress-induced hepatic reactions provided by GdCl? may contribute to its protective effects. ..
  3. Kreiser D, Kelly D, Seidman D, Stevenson D, Baum M, Dennery P. Gestational pattern of heme oxygenase expression in the rat. Pediatr Res. 2003;54:172-8 pubmed
    ..We conclude that there is a clear uterine and placental gestational pattern of HO expression in the rat. This pattern is comparable to that of vascular endothelial growth factor and leptin. ..
  4. Wang T, Sterling H, Shao W, Yan Q, Bailey M, Giebisch G, et al. Inhibition of heme oxygenase decreases sodium and fluid absorption in the loop of Henle. Am J Physiol Renal Physiol. 2003;285:F484-90 pubmed
    ..We conclude that HK intake increases HO-2 expression in the kidney and that HO-dependent metabolites of heme, presumably CO, play a significant role in the regulation of Na+ transport in the loop of Henle. ..
  5. McCoubrey W, Ewing J, Maines M. Human heme oxygenase-2: characterization and expression of a full-length cDNA and evidence suggesting that the two HO-2 transcripts may differ by choice of polyadenylation signal. Arch Biochem Biophys. 1992;295:13-20 pubmed
    ..Further, the fusion protein expressed in Escherichia coli displayed significant heme oxygenase activity, which was inhibited by Zn- and Sn-protoporphyrins, known inhibitors of eukaryotic heme oxygenase, but not by sulfhydryl reagents. ..
  6. Berradi H, Bertho J, Dudoignon N, Mazur A, Grandcolas L, Baudelin C, et al. Renal anemia induced by chronic ingestion of depleted uranium in rats. Toxicol Sci. 2008;103:397-408 pubmed publisher
    ..Spleen erythropoiesis and molecules involved in erythrocyte degradation were also modified by chronic DU exposure. ..
  7. Koike E, Hirano S, Shimojo N, Kobayashi T. cDNA microarray analysis of gene expression in rat alveolar macrophages in response to organic extract of diesel exhaust particles. Toxicol Sci. 2002;67:241-6 pubmed
    ..Our results suggest that cDNA microarray analysis is a useful tool to investigate the biological responses to pulmonary toxicants. ..
  8. Weng Y, Yang G, Weiss S, Dennery P. Interaction between heme oxygenase-1 and -2 proteins. J Biol Chem. 2003;278:50999-1005 pubmed
    ..We speculate that this HO-1.HO-2 protein interaction may promote non-enzymatic functions of HO. ..
  9. Wang H, Garvin J, D Ambrosio M, Falck J, Leung P, Liu R, et al. Heme oxygenase metabolites inhibit tubuloglomerular feedback in vivo. Am J Physiol Heart Circ Physiol. 2011;300:H1320-6 pubmed publisher
    ..We concluded that HO-1 and HO-2 in the nephron inhibit TGF by releasing CO and biliverdin. The inhibitory effect of CO on TGF is mediated by the sGC/cGMP signaling pathway, whereas biliverdin probably acts by reducing O(2)(-). ..

More Information


  1. Boehning D, Sedaghat L, Sedlak T, Snyder S. Heme oxygenase-2 is activated by calcium-calmodulin. J Biol Chem. 2004;279:30927-30 pubmed
    ..Calcium-calmodulin provides a mechanism for rapid and transient activation of HO2 during neuronal activity. ..
  2. Williams S, Wootton P, Mason H, Bould J, Iles D, Riccardi D, et al. Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science. 2004;306:2093-7 pubmed
    ..Furthermore, carotid body cells demonstrated HO-2-dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation. ..
  3. D Agostino D, Mazza E, Neubauer J. Heme oxygenase is necessary for the excitatory response of cultured neonatal rat rostral ventrolateral medulla neurons to hypoxia. Am J Physiol Regul Integr Comp Physiol. 2009;296:R102-18 pubmed publisher
    ..Consistent with this observation, HO-2 expression was present only in the hypoxia-excited neurons. We conclude that RVLM neurons are excited by hypoxia via a heme oxygenase-dependent mechanism. ..
  4. Fan W, Dong W, Leng S, Li D, Cheng S, Li C, et al. Expression and colocalization of NADPH-diaphorase and heme oxygenase-2 in trigeminal ganglion and mesencephalic trigeminal nucleus of the rat. J Mol Histol. 2008;39:427-33 pubmed publisher
    ..3% in TG and 97.6% in MTN. The remarkable parallels between NADPH-d and HO-2 suggest that NO and CO are likely neurotransmitters and mediate the orofacial nociception and sensory feedback of the masticatory reflex arc together. ..
  5. Cella M, Farina M, Keller Sarmiento M, Chianelli M, Rosenstein R, Franchi A. Heme oxygenase-carbon monoxide (HO-CO) system in rat uterus: effect of sexual steroids and prostaglandins. J Steroid Biochem Mol Biol. 2006;99:59-66 pubmed
    ..In addition, these results suggest that uterine HO activity could regulate uterine quiescence in pregnancy via cGMP and it may contribute to the defense against oxidative stress. ..
  6. Zhuang H, Littleton Kearney M, DORE S. Characterization of heme oxygenase in adult rodent platelets. Curr Neurovasc Res. 2005;2:163-8 pubmed
    ..Further investigation into the functional properties of HO itself, heme degradation, and heme bioactive metabolites remains to be conducted to determine the role of HO on platelet dynamics and on microvasculature. ..
  7. Fan W, Huang F, Dong W, Gao Z, Li C, Zhu X, et al. Distribution of heme oxygenase-2 and NADPH-diaphorase in the spinal trigeminal nucleus of the rat. J Mol Histol. 2009;40:209-15 pubmed publisher
    ..The expression and distribution of NADPH-d and HO-2 suggest that NO and CO are likely neurotransmitters and might function in the processing orofacial signal in the STN together. ..
  8. Govindaraju V, Teoh H, Hamid Q, Cernacek P, Ward M. Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered aortic reactivity after hypoxia in rats. Am J Physiol Heart Circ Physiol. 2005;288:H962-70 pubmed
    ..HO-2 is expressed by aortic endothelial cells early during hypoxic exposure and impairs ET-1-mediated potentiation of contraction to alpha-adrenoceptor stimulation. ..
  9. Maines M, Panahian N. The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have different functions?. Adv Exp Med Biol. 2001;502:249-72 pubmed
  10. Posa A, Kupai K, Ménesi R, Szalai Z, Szabó R, Pintér Z, et al. Sexual dimorphism of cardiovascular ischemia susceptibility is mediated by heme oxygenase. Oxid Med Cell Longev. 2013;2013:521563 pubmed publisher
    ..In conclusion, the increased HO activity and expression in females might play a role in the sexual dimorphism of cardiovascular ischemia susceptibility during the reproductive age. ..
  11. Rotenberg M, Maines M. Isolation, characterization, and expression in Escherichia coli of a cDNA encoding rat heme oxygenase-2. J Biol Chem. 1990;265:7501-6 pubmed
    ..Finally, computer analysis of the heme oxygenase-2 cDNA sequence indicates that the predicted amino acid sequence and hydropathy profile of the heme oxygenase-2 protein exhibit similarity with heme oxygenase-1. ..
  12. Hinojos C, Boerwinkle E, Fornage M, Doris P. Combined genealogical, mapping, and expression approaches to identify spontaneously hypertensive rat hypertension candidate genes. Hypertension. 2005;45:698-704 pubmed
    ..The present approach identifies a number of genes that may influence blood pressure in SHR by virtue of allelic effects on gene expression. ..
  13. Farhangkhoee H, Khan Z, Mukherjee S, Cukiernik M, Barbin Y, Karmazyn M, et al. Heme oxygenase in diabetes-induced oxidative stress in the heart. J Mol Cell Cardiol. 2003;35:1439-48 pubmed
    ..These results provide evidence of pro-oxidant activity of HO in the heart in diabetes, which could be mediated by increased redox-active iron. ..
  14. Piotrkowski B, Monzón C, Pagotto R, Reche C, Besio M, Cymeryng C, et al. Effects of heme oxygenase isozymes on Leydig cells steroidogenesis. J Endocrinol. 2009;203:155-65 pubmed publisher
    ..present study, we demonstrate the expression of heme oxygenase (HO) isozymes, HO-1 and HO-2 (listed as HMOX1 and HMOX2 in the MGI Database), in MA-10 Leydig tumor cells and its effect on steroidogenesis...
  15. Kotsiuba A, Chertok M. [The distribution of heme oxygenase-2 in the brainstem nuclei of rats]. Morfologiia. 2012;142:15-9 pubmed
    ..HO-2-positive cells were found 3-5 times more frequently in the sensory nuclei as compared to the motor ones. At the same time, relatively large number of nuclei was detected, which contained either no or a few HO-2-positive neurons. ..
  16. Robison C, McHenry J, Hull E. Increased expression of carbon monoxide-producing enzymes in the MPOA after sexual experience in male rats. Physiol Behav. 2017;171:149-157 pubmed publisher
    ..Together, these findings suggest that endogenous CO may be behaviorally relevant within the MPOA and that CO and NO may be differentially regulated there. ..
  17. Xia C, Jiang R. [Expressions of HO-1 and HO-2 in the vaginal smooth muscle of ovariectomized female rats]. Zhonghua Nan Ke Xue. 2009;15:110-4 pubmed
    ..Estrogen may play a physiological role in the vaginal smooth muscle via HO/CO. ..
  18. Ding B, Gibbs P, Brookes P, Maines M. The coordinated increased expression of biliverdin reductase and heme oxygenase-2 promotes cardiomyocyte survival: a reductase-based peptide counters ?-adrenergic receptor ligand-mediated cardiac dysfunction. FASEB J. 2011;25:301-13 pubmed publisher
    ..Finding that BVR and HO-2 levels, myocyte apoptosis, and contractile function of the heart can be modulated by small human BVR-based peptides offers a promising therapeutic approach for treatment of cardiac dysfunctions. ..
  19. Sharma H, Westman J. 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. Acta Neurochir Suppl. 2003;86:389-94 pubmed
  20. Sun M, Zhong M, Gu J, Qian F, Gu J, Chen H. Effects of different levels of exercise volume on endothelium-dependent vasodilation: roles of nitric oxide synthase and heme oxygenase. Hypertens Res. 2008;31:805-16 pubmed publisher
    ..Elevations of vascular eNOS and HO-1/HO-2 may contribute to enhanced vasodilation, which can be offset by intense training and elevation in vascular iNOS. ..
  21. Sutherland B, Rahman R, Clarkson A, Shaw O, Nair S, Appleton I. Cerebral heme oxygenase 1 and 2 spatial distribution is modulated following injury from hypoxia-ischemia and middle cerebral artery occlusion in rats. Neurosci Res. 2009;65:326-34 pubmed publisher
    ..This report of HO-2 protein expression upregulation following HI coupled with an increase in HO-1 immunoreactivity suggests that this response may be implicated in reducing cell death or repairing damage induced by cerebral ischemia. ..
  22. Chen Z, Xu H, Haimano S, Li X, Li X. Quetiapine and venlafaxine synergically regulate heme oxygenase-2 protein expression in the hippocampus of stressed rats. Neurosci Lett. 2005;389:173-7 pubmed
    ..These data suggest that both quetiapine and venlafaxine share the hippocampus as their common target by enhancing hippocampal resilience, which may be impaired in patients with schizophrenia or depression. ..
  23. Barreiro E, Comtois A, Mohammed S, Lands L, Hussain S. Role of heme oxygenases in sepsis-induced diaphragmatic contractile dysfunction and oxidative stress. Am J Physiol Lung Cell Mol Physiol. 2002;283:L476-84 pubmed
    ..We conclude that both HO-1 and HO-2 proteins play an important role in the regulation of muscle contractility and in the defense against sepsis-induced oxidative stress. ..
  24. McCoubrey W, Maines M. The structure, organization and differential expression of the gene encoding rat heme oxygenase-2. Gene. 1994;139:155-61 pubmed
    ..9 kb), the larger of which is translated less efficiently than the smaller. Presently, we show that the transcripts are the products of a single gene and differ in the use of the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  25. Cruse I, Maines M. Evidence suggesting that the two forms of heme oxygenase are products of different genes. J Biol Chem. 1988;263:3348-53 pubmed
    ..The secondary structure prediction analysis revealed an area of 100% structural homology with only 72% sequence homology. We predict this region may represent the catalytic site of the enzyme. ..
  26. Remmers E, Griffiths M, Longman R, Gulko P, Kawahito Y, Chen S, et al. An integrated rat genetic map: analysis of linkage conservation with the mouse and human maps. Transplant Proc. 1999;31:1549-54 pubmed