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Peroxynitrite-induced apoptosis in HL-60 cells
1Department of Cell Biology, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084, USA.
The Journal of Biological Chemistry
|July 14, 1995
Summary
Peroxynitrite (ONOO-), a potent oxidant, induces apoptosis in leukemia cells like HL-60 and U-937. This oxidant is ineffective against normal cells, suggesting a targeted role in cancer cell death.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Peroxynitrite (ONOO-) is a reactive nitrogen species formed from nitric oxide (NO) and superoxide.
- It is a potent oxidant with potential roles in cellular damage and signaling.
Purpose of the Study:
- To investigate the effect of peroxynitrite on apoptosis in different cell lines.
- To determine the concentration- and time-dependence of peroxynitrite-induced apoptosis.
Main Methods:
- Exposure of HL-60 and U-937 cells to varying concentrations of peroxynitrite.
- Analysis of apoptosis using DNA fragmentation assays and propidium iodide staining.
- Comparison of effects on transformed versus normal cells (endothelial and peripheral blood mononuclear cells).
Main Results:
- Peroxynitrite induced apoptosis in HL-60 and U-937 cells in a time- and concentration-dependent manner.
- Apoptosis was evidenced by DNA laddering, DNA fragmentation assays, and chromatin condensation.
- Normal endothelial and peripheral blood mononuclear cells were resistant to peroxynitrite-induced apoptosis.
Conclusions:
- Peroxynitrite is a potent inducer of apoptosis in specific cancer cell lines.
- This oxidant demonstrates selective toxicity towards transformed cells over normal cells.
- Peroxynitrite has a newly implicated function as an inducer of apoptosis.