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

Abstract

This study examined the role of heme oxygenase (HO) in the acquisition of resistance to hydrogen peroxide (H 2O 2) and hemin toxicity by renal epithelial cells (BSC-1). BSC-1 cells adapted by long-term exposure to H 20 2 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 H 2O 2 induced HO-1 mRNA. When cells were exposed to H 20 2 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 H 20 2. 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, H 20 2 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.