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

Desire Tshala-Katumbay, Victor Monterroso, Robert Kayton, Michael Lasarev, Mohammad Sabri, Peter Spencer

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Neuroprotein changes in the spinal cord of rodents with aliphatic γ-diketone axonopathy induced by 2,5-hexanedione (2,5-HD) are compared with those reported previously in aromatic γ-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 1α, 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.

Original languageEnglish (US)
Pages (from-to)482-489
Number of pages8
JournalToxicological Sciences
Volume107
Issue number2
DOIs
Publication statusPublished - Feb 5 2009

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Keywords

  • Axonopathy
  • Biomarkers
  • Neurodegeneration
  • Proteomics
  • Solvent neurotoxicity
  • γ-diketones

ASJC Scopus subject areas

  • Toxicology

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