Dual role of heme oxygenase in epithelial cell injury: contrasting effects of short-term and long-term exposure to oxidant stress.
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.
da Silva
J L
JL
The Rockefeller University, New York 10021, USA.
Morishita
T
T
Escalante
B
B
Staudinger
R
R
Drummond
G
G
Goligorsky
M S
MS
Lutton
J D
JD
Abraham
N G
NG
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
D012333:RNA, Messenger; D006418:Heme; D006427:Hemin; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing)