title: Increased capacity for glutathione synthesis enhances resistance to radiation in Escherichia coli: a possible model for mammalian cell protection.
abstract: A strain of Escherichia coli, enriched in its content of gamma-glutamylcysteine synthetase and glutathione synthetase activities by recombinant DNA techniques, is more resistant to the lethal effects of gamma-irradiation than is the corresponding wild strain. Although the gene-enriched strain has higher glutathione levels than the wild strain, the observed radioresistance appears to be associated with the increased capacity of the gene-enriched strain to synthesize glutathione when irradiated rather than to the cellular levels of glutathione per se. Thus, resistance was abolished in the presence of buthionine sulfoximine, a selective inactivator of gamma-glutamylcysteine synthetase that decreases glutathione synthesis but that does not act directly to lower cellular glutathione levels. Conclusions drawn from studies on this E. coli model system may have relevance to protection of mammalian cells by glutathione.
authors.affiliation: Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
authors.forename: W R
authors.initials: WR
authors.lastname: Moore
authors.forename: M E
authors.initials: ME
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Meister
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: A
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D004274:DNA, Recombinant / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects*; D005720:Gamma Rays; D005721:Glutamate-Cysteine Ligase / Q000235:genetics* / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D005981:Glutathione Synthase / Q000235:genetics* / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008954:Models, Biological; D010453:Peptide Synthases / Q000235:genetics*; D011835:Radiation Protection; D013045:Species Specificity
chemical_list: D000963:Antimetabolites; D004274:DNA, Recombinant; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D010453:Peptide Synthases; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione