Abstract
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: γ-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 γ-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. Copyright (C) 2000 Elsevier Science Inc.
Original language | English (US) |
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Pages (from-to) | 447-462 |
Number of pages | 16 |
Journal | Free Radical Biology and Medicine |
Volume | 28 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 2000 |
Keywords
- DNA oxidation
- Free radicals
- Knockout mice
- Lipid peroxidation
- Liver
- Metallothionein
- Protein oxidation
ASJC Scopus subject areas
- Physiology (medical)
- Biochemistry