The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

HMOX1  -  heme oxygenase (decycling) 1

Bos taurus

 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of HMOX1

 

Psychiatry related information on HMOX1

 

High impact information on HMOX1

  • Here, we report that up-regulation of HO-1 in aortic endothelial cells by severe hypoxic conditions (pO(2) </= 2 mm Hg) is preceded by increased inducible NO synthase and NO synthase activity [1].
  • We suggest that in addition to oxidative stress, HO-1 gene expression can be regulated by redox reactions involving NO and S-nitrosothiols (nitrosative stress), emphasizing a versatile role for the heme oxygenase pathway in the cellular adaptation to a variety of stressful conditions [1].
  • A series of antioxidant agents did not prevent the elevation in heme oxygenase activity by hypoxia; however, the precursor of glutathione synthesis and thiol donor, N-acetylcysteine, completely abolished HO-1 induction [1].
  • These results indicate that intracellular interaction of thiols with NO is an important determinant in the mechanism leading to HO-1 induction by reduced oxygen levels [1].
  • Preincubation of Fraction II with 0.5 mM diethylpyrocarbonate inactivates heme oxygenase in the reconstituted system, and 10 microM mesohemin partially protects this Fraction against diethylpyrocarbonate inactivation [3].
 

Chemical compound and disease context of HMOX1

  • Hypoxia (18 h) also caused a significant (P < 0.05) increase in heme oxygenase activity which was markedly potentiated by the presence of low concentrations of curcumin (5 microM) [4].
  • Addition of the Fe(3+) chelator desferrioxamine mesylate (DFO) or the Fe(2+) chelator o-phenanthroline during hypoxia alone or during the entire H/R period inhibited the induction of HO activity and HO-1 protein levels [5].
 

Biological context of HMOX1

  • Se-sufficient BAECs up-regulated HO-1 expression following stimulation with the pro-oxidant, 15-HPETE (15-hydroperoxyeicosatetraenoic acid), and levels of this antioxidant inversely correlated with EC apoptosis [6].
  • These results suggested that not only ortho-dihydroxyl groups but also aromatic ester and methoxyl ester moieties are necessary for full HO-1 induction and cytoprotection against toxic tBHP-derived ROS [7].
  • By use of Western blotting, cell viability analysis, and antisense technique, the present study investigates the involvement of HO-1 in endothelial protection induced by the clinically used nitric oxide (NO) donor molsidomine (specifically, its active metabolite 3-morpholinosydnonimine [SIN-1]) and the second messenger cGMP [8].
  • The phenotypes of mutant HO1 were found to result from a single amino acid replacement of ArpA; the proline residue at position 115 in the wild-type ArpA was replaced by serine, yielding mutant ArpA (P115S) [9].
  • Since consensus sequences for the antioxidant response element (ARE) are found in the promoters of the gamma-GCS and HO-1 genes, we examined nuclear translocation of Nrf2, a CNC-bZIP protein which binds to and activates the ARE [10].
 

Anatomical context of HMOX1

  • Using an oxidant stress model based on Se deficiency in BAECs (bovine aortic endothelial cells), we sought to determine whether TrxR1 activity may contribute to the differential regulation of HO-1 expression as a function of altered redox environment [6].
  • In bovine pulmonary artery endothelial cells, SIN-1 and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) at 1 to 100 micromol/L induced the synthesis of HO-1 protein in a concentration-dependent fashion up to 3-fold over basal levels [8].
  • These results demonstrate that HO-1 gene transfer does not affect endothelial and smooth muscle function of normal arteries, and that expression of recombinant HO-1 in cerebral arteries protects vasomotor function against OxyHb-induced injury [11].
  • Thus we have identified novel mechanisms related to the induction of HO-1 by NO indicating that the signalling actions of NO vary significantly in the presence of haem and haem metabolites, ultimately increasing the defensive abilities of the endothelium to counteract oxidative and nitrosative stress [12].
  • In the present study, we examined the dynamics of HO-1 expression and bilirubin production after stimulation of vascular smooth-muscle cells with hemin, a potent inducer of the HO-1 gene [13].
 

Associations of HMOX1 with chemical compounds

  • Reduced selenoprotein activity during dietary selenium (Se) deficiency can result in a compensatory increase of other non-Se-dependent antioxidants, such as HO-1 (haem oxygenase-1) that may help to counteract the damaging effects of oxidant stress [6].
  • While Se-deficient BAECs exhibited higher basal levels of HO-1, it was not up-regulated upon 15-HPETE treatment, which resulted in significantly higher levels of pro-apoptotic markers [6].
  • Metals such as Pt2+ and Hg2+ strongly inhibited the activity of the reconstituted heme oxygenase system, but the principal site of action of these metals was at the level of NADPH-cytochrome c reductase or biliverdin reductase [14].
  • In vitro heme oxygenase activity requires the presence of all three fractions, plus substrate, O2, reduced pyridine nucleotide, and another reductant [3].
  • Similarly --SH inactivating reagents, such as p-chloromercuribenzoate, 5,5'-dithiobis-(2-nitrobenzoate), or N-ethylmaleimide inhibited the reaction catalyzed by the reconstituted heme oxygenase system principally by inhibiting the activity of NADPH-cytochrome c reductase [14].
 

Other interactions of HMOX1

  • Finally, restoring intracellular levels of the reduced substrate Trx (thioredoxin) in Sedeficient BAECs was sufficient to increase HO-1 activation following 15-HPETE stimulation [6].
  • Our results demonstrate that SIN-1 produces a long-term endothelial protection against cellular injury by TNF-alpha, presumably via a cyclic GMP-dependent pathway leading to up-regulation of protective proteins such as heme oxygenase [15].
 

Analytical, diagnostic and therapeutic context of HMOX1

References

  1. Endothelial heme oxygenase-1 induction by hypoxia. Modulation by inducible nitric-oxide synthase and S-nitrosothiols. Motterlini, R., Foresti, R., Bassi, R., Calabrese, V., Clark, J.E., Green, C.J. J. Biol. Chem. (2000) [Pubmed]
  2. Differential activation of heme oxygenase-1 by chalcones and rosolic acid in endothelial cells. Foresti, R., Hoque, M., Monti, D., Green, C.J., Motterlini, R. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  3. Algal heme oxygenase from Cyanidium caldarium. Partial purification and fractionation into three required protein components. Cornejo, J., Beale, S.I. J. Biol. Chem. (1988) [Pubmed]
  4. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Motterlini, R., Foresti, R., Bassi, R., Green, C.J. Free Radic. Biol. Med. (2000) [Pubmed]
  5. Regulation of endothelial heme oxygenase activity during hypoxia is dependent on chelatable iron. Ryter, S.W., Si, M., Lai, C.C., Su, C.Y. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  6. Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells. Trigona, W.L., Mullarky, I.K., Cao, Y., Sordillo, L.M. Biochem. J. (2006) [Pubmed]
  7. Cytoprotective effects of heme oxygenase-1 induction by 3-O-caffeoyl-1-methylquinic acid. Kweon, M.H., Jung, M.J., Sung, H.C. Free Radic. Biol. Med. (2004) [Pubmed]
  8. Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Polte, T., Abate, A., Dennery, P.A., Schröder, H. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  9. A mutation at proline-115 in the A-factor receptor protein of Streptomyces griseus abolishes DNA-binding ability but not ligand-binding ability. Onaka, H., Sugiyama, M., Horinouchi, S. J. Bacteriol. (1997) [Pubmed]
  10. Nitric oxide stimulates Nrf2 nuclear translocation in vascular endothelium. Buckley, B.J., Marshall, Z.M., Whorton, A.R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  11. Protective effect of heme oxygenase-1 gene transfer against oxyhemoglobin-induced endothelial dysfunction. Eguchi, D., Weiler, D., Alam, J., Nath, K., Katusic, Z.S. J. Cereb. Blood Flow Metab. (2001) [Pubmed]
  12. Haem and nitric oxide: synergism in the modulation of the endothelial haem oxygenase-1 pathway. Foresti, R., Hoque, M., Bains, S., Green, C.J., Motterlini, R. Biochem. J. (2003) [Pubmed]
  13. Dynamics of haem oxygenase-1 expression and bilirubin production in cellular protection against oxidative stress. Clark, J.E., Foresti, R., Green, C.J., Motterlini, R. Biochem. J. (2000) [Pubmed]
  14. Purification and properties of bovine spleen heme oxygenase. Amino acid composition and sites of action of inhibitors of heme oxidation. Yoshinaga, T., Sassa, S., Kappas, A. J. Biol. Chem. (1982) [Pubmed]
  15. The nitric oxide donor SIN-1 protects endothelial cells from tumor necrosis factor-alpha-mediated cytotoxicity: possible role for cyclic GMP and heme oxygenase. Polte, T., Oberle, S., Schröder, H. J. Mol. Cell. Cardiol. (1997) [Pubmed]
  16. Structural studies on bovine spleen heme oxygenase. Immunological and structural diversity among mammalian heme oxygenase enzymes. Schacter, B.A., Cripps, V., Troxler, R.F., Offner, G.D. Arch. Biochem. Biophys. (1990) [Pubmed]
 
WikiGenes - Universities