Re-partitioning of Cu and Zn isotopes by modified protein expression

Anette Büchl, Chris J. Hawkesworth, K. Vala Vala, David R. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Cu and Zn have naturally occurring non radioactive isotopes, and their isotopic systematics in a biological context are poorly understood. In this study we used double focussing mass spectroscopy to determine the ratios for these isotopes for the first time in mouse brain. The Cu and Zn isotope ratios for four strains of wild-type mice showed no significant difference (δ65Cu -0.12 to -0.78 permil; δ66Zn -0.23 to -0.48 permil). We also looked at how altering the expression of a single copper binding protein, the prion protein (PrP), alters the isotope ratios. Both knockout and overexpression of PrP had no significant effect on the ratio of Cu isotopes. Mice brains expressing mutant PrP lacking the known metal binding domain have δ65Cu isotope values of on average 0.57 permil higher than wild-type mouse brains. This implies that loss of the copper binding domain of PrP increases the level of 65Cu in the brain. δ66Zn isotope values of the transgenic mouse brains are enriched for 66Zn to the wild-type mouse brains. Here we show for the first time that the expression of a single protein can alter the partitioning of metal isotopes in mouse brains. The results imply that the expression of the prion protein can alter cellular Cu isotope content.

Original languageEnglish
Article number11
JournalGeochemical Transactions
Volume9
DOIs
Publication statusPublished - 10 Oct 2008

Bibliographical note

Funding Information:
This study was supported by the Leverhulme Trust (ID 20010681) and the Quality of Life (Environment) 5th framework programme of the European Commission (FATEPRIDE QLRT – 2001 – 02723). We thank Corey Archer and Derek Vance for their support in the laboratory, and Corey Archer for his comments on the manuscript. The authors also thank Andrew Ward for the Harry mice and Charles Weissmann for the PrP transgenic mice.

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