title: 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 (H2O2) and hemin toxicity by renal epithelial cells (BSC-1). BSC-1 cells adapted by long-term exposure to H2O2 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 H2O2. 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, H2O2 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.
authors.affiliation: The Rockefeller University, New York 10021, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: da Silva
authors.forename: T
authors.initials: T
authors.lastname: Morishita
authors.forename: B
authors.initials: B
authors.lastname: Escalante
authors.forename: R
authors.initials: R
authors.lastname: Staudinger
authors.forename: G
authors.initials: G
authors.lastname: Drummond
authors.forename: M S
authors.initials: MS
authors.lastname: Goligorsky
authors.forename: J D
authors.initials: JD
authors.lastname: Lutton
authors.forename: N G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006418:Heme / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D006418:Heme; D006427:Hemin; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing)