Probing mechanisms of axonopathy. Part II: Protein targets of 2,5-hexanedione, the neurotoxic metabolite of the aliphatic solvent n-hexane.
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.
Tshala-Katumbay
Desire
D
Department of Neurology, Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon 97239, USA. tshalad@ohsu.edu
Monterroso
Victor
V
Kayton
Robert
R
Lasarev
Michael
M
Sabri
Mohammad
M
Spencer
Peter
P
D000098:Acetophenones / Q000633:toxicity; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000473:pathology*; D015415:Biomarkers; D048430:Cell Shape / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006586:Hexanes / Q000493:pharmacokinetics / Q000633:toxicity*; D006588:Hexanones / Q000633:toxicity*; D007525:Isoelectric Focusing; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000098:Acetophenones; D000596:Amino Acids; D015415:Biomarkers; D006586:Hexanes; D006588:Hexanones; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009498:Neurotoxins; C026385:n-hexane; C048792:1,2-diacetylbenzene; C011269:2,5-hexanedione