Original article
Dual role of heme oxygenase in epithelial cell injury: Contrasting effects of short-term and long-term exposure to oxidant stress

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Abstract

This study examined the role of heme oxygenase (HO) in the acquisition of resistance to hydrogen peroxide (H2O2) and hemin toxicity by renal epithelial cells (BSC-1). BSC-1 cells adapted by long-term exposure to H202 exhibited a twofold increase in basal HO activity and expression of HO-1 mRNA as compared with their wild-type counterparts. Exposure of both adapted and wild-type BSC-1 cells to H2O2 induced HO-1 mRNA. When cells were exposed to H202 for 24 hours, cell viability was reduced; however, an inhibitor of HO activity, Zn 2,4-bis-glycol protoporphyrin IX, improved cell viability. In a similar manner, ZnDBG completely overcame the reduction in cell viability brought about by 1 hour of hemin treatment. In addition, cells preexposed to hemin for 24 hours maintained a high level of HO mRNA and acquired resistance to further challenge with H202. Hemin treatment per se was associated with a detectable reduction in BSC-1 cell viability; however, the effect of hemin was not additive to the cytotoxicity of hydrogen peroxide, suggesting a common pathway of cell injury. In conclusion, two interrelated stressors, H202 and hemin, produced a stimulation of HO-1, and this was associated with a reduction in the viability of BSC-1 cells. Long-term exposure (24 hours) to both stressors resulted in the acquisition of some resistance to a further acute challenge of oxidant stress in BSC-1 cells.

References (38)

  • GR Guy et al.

    Inactivation of a redoxsensitive protein phosphatase during the early events of tumor necrosis factor/interleukin-1 signal transduction

    J Biol Chem

    (1993)
  • GF Vile et al.

    Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin

    J Biol Chem

    (1993)
  • G Balla et al.

    Ferritin: a cytoprotective antioxidant strategen of endothelium

    J Biol Chem

    (1992)
  • J Neuzil et al.

    Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol inhibiting plasma and low density lipoprotein lipid peroxidation

    J Biol Chem

    (1994)
  • SM Keyse et al.

    Heme oxygenase is the major 32 kDA stress protein induced in human skin fibroblasts by UV radiation, hydrogen peroxide, and sodium arsenite

  • NG Abraham et al.

    Transfection of the human heme oxygenase into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity

  • O Stocker et al.

    Bilirubin is an antioxidant of possible physiological importance

    Science

    (1987)
  • K Mitani et al.

    The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat shock protein 70 in human hepatoma cells

    Biochem J

    (1993)
  • MD Kappas et al.

    Metals as regulators of heme metabolism

    Science

    (1976)
  • Cited by (0)

    Supported, in part, by NIH Grants HL-54138 and DK-45695 and by the Cantigny Research Foundation Inc.

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