Format

Send to

Choose Destination
Toxicol Sci. 2009 Feb;107(2):482-9. doi: 10.1093/toxsci/kfn241. Epub 2008 Nov 25.

Probing mechanisms of axonopathy. Part II: Protein targets of 2,5-hexanedione, the neurotoxic metabolite of the aliphatic solvent n-hexane.

Author information

1
Department of Neurology, Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon 97239, USA. tshalad@ohsu.edu

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.

PMID:
19033394
PMCID:
PMC2639756
DOI:
10.1093/toxsci/kfn241
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center