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Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia.

Abstract
Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins with potential antioxidant activity. Despite evidence that they are upregulated in pulmonary tissue after oxidative stress, little is known regarding their influence on trace metal homeostasis. In this study, we have used copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpressing and gene knockout mice and hyperoxia to investigate the effects of chronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and metallothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copper and iron as well as circulating copper homeostasis. These results suggest that ceruloplasmin and metallothionein may function as antioxidants independent of their role in trace metal homeostasis and that Cu/Zn SOD functions in copper homeostasis via mechanisms distinct from its superoxide scavenging properties.
AuthorsM A Levy, Y H Tsai, A Reaume, T M Bray
JournalAmerican journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 281 Issue 1 Pg. L172-82 (Jul 2001) ISSN: 1040-0605 [Print] United States
PMID11404260 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Metalloproteins
  • Copper
  • Ferritins
  • Metallothionein
  • Iron
  • Superoxide Dismutase
  • Ceruloplasmin
  • Zinc
Topics
  • Animals
  • Antioxidants (metabolism)
  • Ceruloplasmin (metabolism)
  • Copper (metabolism)
  • Ferritins (metabolism)
  • Homeostasis (physiology)
  • Hyperoxia (metabolism)
  • Iron (metabolism)
  • Liver (metabolism)
  • Lung (metabolism)
  • Male
  • Metalloproteins (metabolism)
  • Metallothionein (metabolism)
  • Mice
  • Mice, Knockout (genetics)
  • Superoxide Dismutase (genetics, physiology)
  • Zinc (metabolism)

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