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Induction of glutathione synthetase by 1,10-phenanthroline
1Department of Molecular Biology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA. suny@aa.wl.com
Abstract:
The differential display (DD) was employed to identify the gene(s) responsible for 1,10-phenanthroline (OP)-induced apoptosis in murine tumor cells (Sun, Y., Bian, J., Wang, Y. and Jacobs, C. (1997) Oncogene 14, 385-393 [1]). An OP-inducible gene was isolated which encodes mouse glutathione synthetase (GSS). The GSS mRNA level began to increase 6 h post OP treatment and remained at a high level thereafter up to 24 h tested. Induction of GSS was found not to be associated with p53 activation. No significant induction of DNA fragmentation was detected in two murine tumor lines upon GSS transfection. This is the first observation indicating that GSS is inducible rather specifically by a metal chelator and that induction of GSS, however, is not sufficient to induce apoptosis. It may merely reflect a cellular response to OP-induced redox disturbance.
Insights
Glutathione synthetase (GSS) is induced by 1,10-phenanthroline in tumor cells, but this induction does not cause apoptosis. GSS induction may reflect a cellular response to redox disturbance.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- 1,10-phenanthroline (OP) is a metal chelator known to induce apoptosis in tumor cells.
- The specific genes involved in OP-induced apoptosis have not been fully elucidated.
- Understanding cellular responses to OP is crucial for cancer research.
Purpose of the Study:
- To identify genes induced by 1,10-phenanthroline (OP) in murine tumor cells.
- To investigate the role of the identified gene in OP-induced apoptosis.
- To explore the relationship between GSS induction and cellular redox balance.
Main Methods:
- Differential display (DD) technique was used to screen for OP-inducible genes.
- Quantitative analysis of GSS mRNA levels following OP treatment.
- Transfection experiments to assess the effect of GSS on apoptosis induction.
- Analysis of p53 activation status.
Main Results:
- A gene encoding mouse glutathione synthetase (GSS) was identified as OP-inducible.
- GSS mRNA levels increased significantly 6 hours post-OP treatment and remained elevated for 24 hours.
- GSS induction was not associated with p53 activation.
- Transfection of GSS did not induce significant DNA fragmentation in tumor cells.
Conclusions:
- Glutathione synthetase (GSS) is specifically inducible by the metal chelator 1,10-phenanthroline.
- GSS induction alone is insufficient to trigger apoptosis in murine tumor cells.
- OP-induced GSS expression likely represents a cellular response to redox disturbances rather than a direct apoptotic pathway.