Human Heme Oxygenase (HO)-1 Deficiency and the Oxidative Injury of Vascular Endothelial Cells

  • A. Yachie
  • T. Toma
  • S. Shimura
  • L. Yue
  • K. Morimoto
  • K. Maruhashi
  • Y. Niida
  • K. Ohta
  • Y. Kasahara
  • Y. Saikawa
  • S. Koizumi

Abstract

Heme oxygenase-1 (HO-1) constitutes one of the three isozymes of HO, which catalyze the degradation of heme into biliverdin, carbon monoxide (CO) and free iron.1, 2, 3, 4, 5 Recent experimental data indicate that one of the heme degradation products, CO acts on cellular metabolism to protect cells from oxidative stress and regulate production of inflammatory molecules.6, 7, 8 As a result, CO directly controls the inflammatory state of a given tissue and at the same time, regulates the level of microcirculation within the target organs acting as a gaseous vasodilator.9, 10, 11 Among three isozymes with similar enzyme activities, HO-1 is the only protein which is rapidly induced upon stimulation with various oxidative stresses.12, 13, 14 Therefore, it is suggested that any defect in its function will lead to uncontrollable inflammatory responses upon certain exogenous insults, such as infection and hemolysis.

Keywords

Codon Recombination Carbon Monoxide Iodide Bilirubin 

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References

  1. 1.
    N.G Abraham, G.S. Drummond, J.D. Lutton, and A. Kappas, The biological significance and physiological role of heme oxygenase, Cell. Physiol. Biochem., 6, 129–168 (1996).CrossRefGoogle Scholar
  2. 2.
    P.A. Dennery, Regulation and role of heme oxygenase in oxidative injury, Cur. Top. Cell. Regul., 36, 181–199 (2000).CrossRefGoogle Scholar
  3. 3.
    L.E. Otterbein and A.M.K. Choi, Heme oxygenase: colors of defence against cellular stress, Am. J. Physiol. Lung. Cell. Mol. Physiol., 279, L1029–1037 (2000).PubMedGoogle Scholar
  4. 4.
    M.D. Maines, Heme oxygenase: function multiplicity, regulatory mechanisms, and clinical applications, FASEB J., 2, 2557–2568 (1988).PubMedGoogle Scholar
  5. 5.
    W.K. McCoubrey Jr., T.J. Huang, and M.D. Maines, Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3, Eur. J. Biochem., 241, 725–732 (1997).CrossRefGoogle Scholar
  6. 6.
    A.M.K. Choi and J. Alam., Heme oxygenase-1: function, regulation and implication of a novel stress-inducible protein in oxidant-induced lung injury, Am. J. Respir. Cell. Mol. Biol., 15, 9–19 (1996).PubMedGoogle Scholar
  7. 7.
    D. Willis, A.R. Moore, R. Frederick, and D.A. Willoughby, Heme oxygenase: a novel target for the modulation of the inflammatory response Nature Med., 2, 87–90 (1996).PubMedCrossRefGoogle Scholar
  8. 8.
    K.D. Poss and S. Tonegawa, Reduced stress defence in heme oxygenase 1-deficient cells, Proc. Natl. Acad. Sci. USA, 94, 10925–10930 (1997).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Suematsu and Y. Ishimura, The heme oxygenase-carbon monoxide system: a regulator of hepatobiliary function, Hepatology, 31, 3–6 (2000).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Suzuki, K. Kanamaru, H. Tsunoda, H. Inada, M. Kuroki H. Sun, S. Waga, and T. Tanaka, Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasms in rats, J. Clin. Invest., 104, 59–66 (1999).PubMedCrossRefGoogle Scholar
  11. 11.
    N. Goda, K. Suzuki, M. Naito, S. Takeoka, E. Tsuchida, Y. Ishimura, T. Tamatani, and M. Suematsu, Distribution of heme oxygenase isoforms in rat liver, J. Clin. Invest., 101, 604–612 (1998).PubMedCrossRefGoogle Scholar
  12. 12.
    K.A. Nath, G. Balla, G.M. Vercellotti, J. Balla, H.S. Jacob, M.D. Levitt, and M.E. Rosenberg, Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat, J. Clin. Invest., 90, 267–270 (1992).PubMedCrossRefGoogle Scholar
  13. 13.
    J. Balla, H.S. Jacob, G. Balla, K. Nath, and G.M. Vercellotti, Endothelial cell heme oxygenase and ferritin induction by heme proteins: a possible mechanism limiting shock damage, Trans. Assoc. Am. Physicians, 105, 1 (1992).PubMedGoogle Scholar
  14. 14.
    F. Amersi, Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury, J. Clin. Invest., 104, 1631–1639 (1999).PubMedCrossRefGoogle Scholar
  15. 15.
    A. Yachie, Y. Niida, T. Wada, N. Igarashi, H. Kaneda, T. Toma, K. Ohta, Y. Kasahara, and S. Koizumi, Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency, J. Clin. Invest., 103, 129 (1999).PubMedCrossRefGoogle Scholar
  16. 16.
    K. Ohta, A. Yachie, K. Fujimoto, H. Kaneda, T. Wada, T. Toma, A. Seno, Y Kasahara, H. Yokoyama, H. Seki, and S. Koizumi, Tubular injury as a cardinal pathological feature in human heme oxygenase-1 deficiency, Am. J. Kidney Dis., 35, 863–870 (2000).PubMedCrossRefGoogle Scholar
  17. 17.
    Y. Saikawa, H. Kaneda, L. Yue, S. Shimura, T. Toma, Y. Kasahara, A. Yachie, and S. Koizumi, Structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in a human case with heme oxygenase-1 deficiency, Human Mut., 16, 178–179 (2000).CrossRefGoogle Scholar
  18. 18.
    S. Shibahara, M. Sato, R.M. Muller, and T. Yoshida, Structural organization of the human heme oxygenase gene and the function of its promoter, Eur. J. Biochem., 171, 557–563 (1988).Google Scholar
  19. 19.
    R.M. Tyrrell, L.A. Applegate, and Y. Tromvoukis, The proximal promoter region of the human heme oxygenase gene contains elements involved in stimulation of transcriptional activity by a variety of agents including oxidants Carcinogenesis 14, 761–765 (1993).PubMedCrossRefGoogle Scholar
  20. 20.
    K. Takeda, S. Ishizawa, M. Sato, T. Yoshida and S. Shibahara, Identification of a cis-acting element that is responsible for cadmium-mediated induction of the human heme oxygenase gene, J. Biol. Chem., 269, 22858–22867 (1994).PubMedGoogle Scholar
  21. 21.
    D.N. Cooper, M. Krawczak, and S.E. Antonarakis, The nature and mechanisms of human gene mutation, in: The Metabolic and Molecular Biology, edited by C.R Scriver, et al. (McGraw-Hill, New York, 1995), pp. 259–291.Google Scholar
  22. 22.
    Y. Miki, Retrotransposal integration of mobile genetic elements in human disease, J. Hum. Genet., 43, 77–84 (1998).PubMedCrossRefGoogle Scholar
  23. 23.
    C.W. Schmid and W.R. Jelinek, The Alu family of dispersed repetitive sequences, Science, 216, 1065–1070 (1982).PubMedCrossRefGoogle Scholar
  24. 24.
    J. Jurka and T. Smith, A fundamental division in the Alu family of repeated sequence, Proc. Natl . Acad. Sci. USA, 85, 4775 (1998).CrossRefGoogle Scholar
  25. 25.
    J. Jurka and A. Milosavljevic, Reconstruction and analysis of human Alu genes, J. Mol. Evol., 32, 105–121 (1991).PubMedCrossRefGoogle Scholar
  26. 26.
    N.S. Rudiger, N. Gregersen, and M.C. Kielland-Brandt, One short well conserved region of Alusequences is involved in human gene rearrangements and has homology with prokaryotic chi, Nucleic Acids Res., 23, 256–260 (1995).PubMedCrossRefGoogle Scholar
  27. 27.
    M. Onodera, A. Yachie, D.M. Nelson, H. Welchlin, R.A. Morgan, and R.M. Blaese, A simple and reliable method for screening retroviral producer clones without selectable markers, Hum Gene Ther, 8, 1189–1194(1997).PubMedCrossRefGoogle Scholar
  28. 28.
    L.J. Wang, T.S. Lee, F.Y. Lee, R.C. Pai, and L.Y. Chau, Expression of heme oxygenase-1 in atherosclerotic lesions, Am. J. Pathol. 152, 711 (1998).PubMedGoogle Scholar
  29. 29.
    A. Agarwal, H. de Leon, J.B. Laursen, J.N. Wilcox, G. De Keulenaer K.K. Griendling, and R.W. Alexander, Linoleyl hydroperoxide transcriptionally upregulates heme oxygenase-1 gene expression in human renal epithelial cells, J. Am. Soc. Nephrol., 9, 1990–1997 (1998).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • A. Yachie
    • 1
  • T. Toma
    • 2
  • S. Shimura
    • 2
  • L. Yue
    • 2
  • K. Morimoto
    • 2
  • K. Maruhashi
    • 2
  • Y. Niida
    • 2
  • K. Ohta
    • 2
  • Y. Kasahara
    • 2
  • Y. Saikawa
    • 2
  • S. Koizumi
    • 2
  1. 1.Dept. Lab. Sci.Kanazawa Univ.KanazawaJapan
  2. 2.Dept. Pediatr.Kanazawa Univ.KanazawaJapan

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