Using MT(-/-) mice to study metallothionein and oxidative stress.
Mice with null mutations for metallothionein genes MT-1 and MT-2 were used to study the role that metallothionein plays in protecting cellular targets in vivo from oxidative stress. Wild-type (MT(+/+)) and MT-null (MT(-/-)) mice were treated with either saline or zinc and exposed to two types of oxidative stress: gamma-irradiation or 2-nitropropane. There was no alteration in the antioxidant defense system (superoxide dismutase, catalase, or glutathione peroxidase and glutathione levels) to compensate for the lack of the metallothionein in the MT(-/-) mice. The amount of oxidative damage to liver DNA, lipids, and proteins were similar for the MT(-/-) and MT(+/+) mice even though the levels of metallothionein in the livers of the saline- or zinc-pretreated MT(+/+) mice were 5- to 100-fold greater than found in the MT(-/-) mice. To determine if metallothionein can protect mice from the lethal effects of ionizing radiation, the mean survivals of MT(-/-) and MT(+/+) mice exposed to whole body gamma-irradiation were measured and found to be similar. However, the mean survival increased significantly after zinc pretreatment for both the MT(-/-) and MT(+/+) mice. These results demonstrate that tissue levels of metallothionein do not protect mice in vivo against oxidative stress.
Conrad
C C
CC
Department of Molecular Biology and Immunology, The University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
Grabowski
D T
DT
Walter
C A
CA
Sabia
M
M
Richardson
A
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008668:Metallothionein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005974:Glutamate-Ammonia Ligase; D003849:Deoxyguanosine; D005978:Glutathione