Skip Navigation


ToxSci Advance Access originally published online on November 25, 2008
Toxicological Sciences 2009 107(2):482-489; doi:10.1093/toxsci/kfn241
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
107/2/482    most recent
kfn241v1
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 arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tshala-Katumbay, D.
Right arrow Articles by Spencer, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tshala-Katumbay, D.
Right arrow Articles by Spencer, P.
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

Probing Mechanisms of Axonopathy. Part II: Protein Targets of 2,5-Hexanedione, the Neurotoxic Metabolite of the Aliphatic Solvent n-Hexane

Desire Tshala-Katumbay*,{dagger},1, Victor Monterroso{ddagger}, Robert Kayton{dagger}, Michael Lasarev{dagger}, Mohammad Sabri*,{dagger} and Peter Spencer*,{dagger}

* Department of Neurology {dagger} Center for Research on Occupational & Environmental Toxicology {ddagger} Department of Comparative Medicine, School of Medicine, Oregon Health & Science University, Portland, Oregon 97239

1 To whom correspondence should be addressed at Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, 3181 S.W. Jackson Park Road, mail code L606, Portland, OR 97239. Fax: (503) 494-6831. E-mail: tshalad{at}ohsu.edu.

Received October 10, 2008; accepted November 11, 2008


  Abstract

Neuroprotein changes in the spinal cord of rodents with aliphatic {gamma}-diketone axonopathy induced by 2,5-hexanedione (2,5-HD) are compared with those reported previously in aromatic {gamma}-diketone–like axonopathy induced by 1,2-diacetylbenzene (1,2-DAB). Sprague-Dawley rats were treated intraperitoneally with 500 mg/kg/day 2,5-HD, equimolar doses of 2,3-hexanedione (negative control), or an equivalent amount of saline containing 50% dimethyl sulfoxide (vehicle), 5 days a week, for 3 weeks. Analysis of the lumbosacral proteome by 2-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight/tandem mass spectrometry revealed 34 proteins markedly modified by 2,5-HD of which neurofilament triplet L, gelsolin, protein disulfide isomerase, glutathione S-transferase, nicotinamide adenine dinucleotide (reduced) dehydrogenase 1{alpha}, pyruvate kinase, and fatty acid synthase were also modified by 1,2-DAB. The expression of proteins involved in maintaining the physical integrity of the cytoskeleton or controlling the redox and protein-folding mechanisms was reduced, whereas that of proteins supporting energy metabolism was mainly increased. The similarity of the neuroproteomic patterns of 2,5-HD and 1,2-DAB axonopathy suggests common biomarkers and/or mechanisms of neurotoxicity associated with exposure to their parent chemicals, namely the industrial solvents n-hexane and 1,2-diethylbenzene, respectively.

Key Words: axonopathy; biomarkers; {gamma}-diketones; proteomics; solvent neurotoxicity; neurodegeneration.


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.