The Relationship Between Copper, Manganese, and Bovine Brain Prion Proteins: Implications for Trace Mineral Nutrition and Bovine Spongiform Encephalopathy

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Date

2006-11-08

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Abstract

The purpose of this research was to evaluate the relationship between dietary copper and manganese and bovine brain prion proteins. Aberrant prion proteins are the causative infective agent in bovine spongiform encephalopathy and other transmissible spongiform encephalopathies. While the cellular prion protein is purported to bind copper ions, a substitution of copper with manganese on the prion protein causes alterations in the biochemical properties of the prion that are similar to the infective prion. An imbalance in brain copper and manganese that allows for prion bound copper to be replaced by manganese has been implicated in the spontaneous conversion of cellular prions to aberrant prions and the subsequent sporadic forms of transmissible spongiform encephalopathies. Until now these findings have not been tested in the bovine. Thus, the studies reported here were designed to test the hypothesis that a copper deficiency, alone or coupled with high dietary manganese, would result in decreased brain copper and increased brain manganese and subsequently alter the biochemical properties of prion proteins. Considerations were given to animal age and length of exposure as well as imbalances in dietary copper and manganese. We report that brain copper is decreased in copper deficient cattle and brain manganese is slightly increased when exposed to high dietary manganese. The perturbations in brain copper and manganese did not alter prion biochemical properties. Most notably there was no apparent manganese for copper substitution on prion proteins that resulted in increased protease resistance or decreased superoxide dismutase-like activity. Also, the prion associated copper and superoxide dismutase-like activities were significantly lower than values reported from in vitro research. Taken together, these results do not support the hypothesis that perturbations in brain copper and manganese induce biochemical changes to prion proteins. Additionally, these data suggest the relationship between brain prions and copper need to be revaluated in the context of whole animal biology.

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Keywords

bovine, prion, copper, manganese

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Degree

PhD

Discipline

Nutrition

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