Properties of human kidney heme oxygenase: Inhibition by synthetic heme analogues and metalloporphyrins

https://doi.org/10.1016/S0006-291X(88)80274-2Get rights and content

Summary

Heme oxygenase activities in human kidney microsomes were found to be from 0.238 to 0.620 nmol of bilirubin/mg/hr (mean 0.375, SD 0.134), which represent approximately 30% of activities determined for human adult liver. There was interindividual variation in heme oxygenase activity of a 2–5-fold difference. Rabbits were immunized with purified human liver heme oxygenase and the resulting antibody preparation was used to examine the species specificity of the enzyme. Microsomal protein with a molecular weight of 32,000 from human kidney was identified on Western blots by its reaction with the anti-heme oxygenase liver antibody similar to the purified enzyme protein. Thus, a homology exists between human hepatic and kidney heme oxygenase. The enzyme activity was sensitive to inhibition by metalloporphyrins, such as tin-protoporphyrin IX and, to a lesser degree, by zinc and cobalt protoporphyrin IX. In a study of different synthetic heme analogues for in vitro inhibition of heme oxygenase, we found that replacement of iron by zinc in deuteroporphyrin IX 2,4 bis glycol dramatically potentiated the inhibition of heme oxygenase activity. This finding demonstrated that zinc deuteroporphyrin IX 2,4 bis glycol is a most potent inhibitor of heme oxygenase activity.

References (30)

  • YoshinagaT. et al.

    J. Biol. Chem.

    (1982)
  • SassaS. et al.

    Blood

    (1983)
  • AbrahamN.G. et al.

    Int. J. Biochem.

    (1988)
  • DresnerD.L. et al.

    Environ. Res.

    (1982)
  • LeonardT.B. et al.

    Biochem. Pharmacol.

    (1986)
  • PattersonS.E. et al.

    Biochem. Pharmacol.

    (1984)
  • DrummondG.S. et al.

    Archs. Biochem. Biophys.

    (1987)
  • TomaroM.L. et al.

    Biochim. Biophys. Acta.

    (1984)
  • AbrahamN.G. et al.

    Am. J. Med. Sci.

    (1986)
  • TenhunenR. et al.
  • TenhunenR. et al.

    Biochemistry

    (1970)
  • PimstoneN.R. et al.

    J. Clin. Invest.

    (1971)
  • DrummondG.S. et al.
  • KappasA. et al.

    Science

    (1976)
  • SundermanF.W. et al.

    Toxicol. Appl. Pharmacol.

    (1983)
  • Cited by (26)

    • Mutations of human cytochrome P450 reductase differentially modulate heme oxygenase-1 activity and oligomerization

      2011, Archives of Biochemistry and Biophysics
      Citation Excerpt :

      Heme oxygenase-1 (HO-1) is the CYPOR-dependent, stress-inducible, membrane-bound enzyme that breaks heme down to carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. Biliverdin is further degraded to bilirubin by the cytosolic enzyme biliverdin reductase (BVR) [24,25], in human spleen, liver, and kidney [26,27]. The C-terminal transmembrane segment of HO-1 was previously shown to drive high-affinity functional complexation with CYPOR [28] and was recently shown to be crucial for HO-1 oligomerization, thereby contributing to its stability and function [29].

    • Spectroscopic study of protoporphyrin IX zinc(II) encapsulated in sol-gel glass

      2005, Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy
    • Targeting heme oxygenase-1 in the treatment of atherosclerosis

      2005, Drug Discovery Today: Therapeutic Strategies
    View all citing articles on Scopus
    View full text