Using MT(-/-) mice to study metallothionein and oxidative stress

Craig C. Conrad, David T. Grabowski, Christi A. Walter, Marian Sabia, Arlan Richardson

Research output: Contribution to journalArticle

41 Scopus citations

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 languageEnglish (US)
Pages (from-to)447-462
Number of pages16
JournalFree Radical Biology and Medicine
Volume28
Issue number3
DOIs
StatePublished - Feb 1 2000

Keywords

  • DNA oxidation
  • Free radicals
  • Knockout mice
  • Lipid peroxidation
  • Liver
  • Metallothionein
  • Protein oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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