Skip Navigation



ToxSci Advance Access published online on November 12, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn231
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
107/1/182    most recent
kfn231v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Jursa, T.
Right arrow Articles by Smith, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jursa, T.
Right arrow Articles by Smith, D. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Ceruloplasmin Alters The Tissue Disposition And Neurotoxicity Of Manganese, But Not Its Loading Onto Transferrin

Thomas Jursa* and Donald R. Smith*,1

* Department of Environmental Toxicology, University of California, Santa Cruz, CA 95064 USA

1 To whom correspondence should be addressed: Donald R. Smith, Dept. of Environmental Toxicology, UCSC, Santa Cruz, CA 95064; smith{at}etox.ucsc.edu

Received August 21, 2008; revision received October 17, 2008; accepted October 18, 2008


  Abstract

Manganese (Mn) is a redox active element, and while its uptake, disposition, and toxicity in mammals may depend in part on its oxidation state, the proteins affecting manganese oxidation state and speciation in vivo are not well known. Studies have suggested that the oxidase protein ceruloplasmin (Cp) mediates iron and manganese oxidation and loading onto plasma transferrin (Tf), as well as cellular iron efflux. We hypothesized that ceruloplasmin may also affect the tissue distribution and eventual neurotoxicity of manganese. To test this, aceruloplasminemic versus wildtype mice were treated with a single i.p. 54Mn tracer dose, or elevated levels of manganese sub-chronically (0, 7.5, or 15 mg Mn/kg s.c., 3 doses/week for 4 weeks), and evaluated for transferrin-bound manganese, blood manganese partitioning, tissue manganese disposition, and levels of brain glutathione, TBARS, and protein carbonyls as measures of oxidative stress, and open arena activity. Results show that ceruloplasmin does not play a role in the loading of manganese onto plasma transferrin in vivo, or in the partitioning of manganese between the plasma and cellular fractions of whole blood. Ceruloplasmin did, however, affect the retention of manganese in blood and its distribution to tissues, most notably kidney and to a lesser extent brain and lung. Results also indicate that ceruloplasmin interacted with chronic elevated manganese exposures to produce greater levels of brain oxidative stress. These results provide evidence that metal oxidase proteins play an important role in altering neurotoxicity arising from elevated manganese exposures.

Key Words: Manganese; ceruloplasmin; transferrin; oxidation state; neurotoxicity.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.