title: Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane.
abstract: 1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p<0.05; fold change ≥ ± 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Zhenlie
authors.initials: Z
authors.lastname: Huang
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
authors.forename: Jie
authors.initials: J
authors.lastname: Chang
authors.forename: Lingyi
authors.initials: L
authors.lastname: Zhang
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kaviarasan
authors.initials: K
authors.lastname: Subramanian
authors.forename: Sahabudeen Sheik
authors.initials: SS
authors.lastname: Mohideen
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000302:isolation & purification; D040901:Proteomics / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D006842:Hydrocarbons, Brominated; D009419:Nerve Tissue Proteins; C118559:1-bromopropane