Induction of glutathione synthetase by 1,10-phenanthroline.
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.
Sun
Y
Y
Department of Molecular Biology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA. suny@aa.wl.com
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002166:Camptothecin / Q000494:pharmacology; D003001:Cloning, Molecular; D004249:DNA Damage; D053938:DNA Fragmentation; D017931:DNA Primers; D004317:Doxorubicin / Q000494:pharmacology; D004790:Enzyme Induction; D005047:Etoposide / Q000494:pharmacology; D016158:Genes, p53 / Q000235:genetics; D005981:Glutathione Synthase / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D010618:Phenanthrolines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017421:Sequence Analysis; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D010618:Phenanthrolines; D012333:RNA, Messenger; D005047:Etoposide; D004317:Doxorubicin; D005981:Glutathione Synthase; C025205:1,10-phenanthroline; D002166:Camptothecin