Abstract
Heme oxygenase-1 (HO-1) responds to a variety of oxidative stresses. We examined whether HO-1 expression influences pro-thrombotic processes, in which the involvement of oxidative stress has been reported. Since HO-1 knockout mice with a C57/BL6J background were not viable, embryonic cells from HO-1 deficient mice (E11.5) were used. Cell viability, the level of plasminogen activator inhibitor-1 (PAI-1) expression and reactive oxygen species (ROS) generation of HO-1 deficient cells in response to the exposures to hydrogen peroxide and oxidized LDL were compared to those with wild-type cells. We also examined the effects of glutathione (GSH), desferrioxamine (DFO) and diphenyleneiodonium (DPI: an NADPH oxidase inhibitor) as well as of the HO reaction products, bilirubin (BR) and carbon monoxide (CO) on PAI-1 expression and ROS generation. PAI-1 expression and ROS generation were markedly elevated in HO-1 deficient cells compared to wild-type cells. Exposure to oxidized LDL significantly elevated PAI-1 expression and ROS production in HO-1 deficient cells. Interestingly, these increases in HO-1 deficient cells were significantly lowered by BR, CO, GSH and DPI while DFO had little effect. Furthermore, BR and CO were effective to improve viabilities of HO-1 deficient cells. These results suggest that HO-1 may be required to suppress ROS generation and the production of pro-thrombotic molecules such as PAI-1.
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Abbreviations
- C57/BL6J, B6; DCFDA:
-
chloromethyl-2, 7-dichlorofluorescein diacetate
- DFO:
-
desferrioxamine
- DMEM:
-
Dulbecco's modified Eagle's medium
- DPI:
-
diphenylene iodinium
- GSH:
-
glutathione
- HO:
-
heme oxygenase
- LDL:
-
low density lipoprotein
- MCP-1:
-
monocyte chemotactic protein-1
- oxLDL:
-
oxidized LDL
- PAI-1:
-
plasminogen activator inhibitor-1
- PCR:
-
polymerase chain reaction
- ROS:
-
reactive oxygen species
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Matsumoto, H., Ishikawa, K., Itabe, H. et al. Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction. Mol Cell Biochem 291, 21–28 (2006). https://doi.org/10.1007/s11010-006-9190-y
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DOI: https://doi.org/10.1007/s11010-006-9190-y