Proteomic identification of carbonylated proteins in F344 rat hippocampus after 1-bromopropane exposure.
1-Bromopropane (1-BP) is neurotoxic in both experimental animals and humans. Previous proteomic analysis of rat hippocampus implicated alteration of protein expression in oxidative stress, suggesting that oxidative stress plays a role in 1-BP-induced neurotoxicity. To understand this role at the protein level, we exposed male F344 rats to 1-BP at 0, 400, or 1000 ppm for 8h/day for 1 week or 4 weeks by inhalation and quantitated changes in hippocampal protein carbonyl using a protein carbonyl assay, two-dimensional gel electrophoresis (2-DE), immunoblotting, and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). Hippocampal reactive oxygen species and protein carbonyl were significantly increased, demonstrating 1-BP-associated induction of oxidative stress and protein damage. MALDI-TOF-TOF/MS identified 10 individual proteins with increased carbonyl modification (p < 0.05; fold-change ≥ 1.5). The identified proteins were involved in diverse biological processes including glycolysis, ATP production, tyrosine catabolism, GTP binding, guanine degradation, and neuronal metabolism of dopamine. Hippocampal triosephosphate isomerase (TPI) activity was significantly reduced and negatively correlated with TPI carbonylation (p < 0.001; r = 0.83). Advanced glycation end-product (AGE) levels were significantly elevated both in the hippocampus and plasma, and hippocampal AGEs correlated negatively with TPI activity (p < 0.001; r = 0.71). In conclusion, 1-BP-induced neurotoxicity in the rat hippocampus seems to involve oxidative damage of cellular proteins, decreased TPI activity, and elevated AGEs.
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Zhenlie
Z
Huang
Sahoko
S
Ichihara
Shinji
S
Oikawa
Jie
J
Chang
Lingyi
L
Zhang
Kaviarasan
K
Subramanian
Sahabudeen Sheik
SS
Mohideen
Gaku
G
Ichihara
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D006842:Hydrocarbons, Brominated / Q000494:pharmacology; D015151:Immunoblotting; D019570:Inhalation Exposure; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006842:Hydrocarbons, Brominated; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; C118559:1-bromopropane