Strain differences in the proteome of dioxin-sensitive and dioxin-resistant mice treated with 2,3,7,8-tetrabromodibenzo-p-dioxin.
Dioxins cause various toxic effects through the aryl hydrocarbon receptor (AHR) in vertebrates, with dramatic species and strain differences in susceptibility. Although inbred mouse strains C3H/HeJ-lpr/lpr (C3H/lpr) and MRL/MpJ-lpr/lpr (MRL/lpr) are known as dioxin-sensitive and dioxin-resistant mice, respectively, the molecular mechanism underlying this difference remains unclear. The difference in the hepatic proteome of the two mouse strains treated with vehicle or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was investigated by a proteomic approach of two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF). To confirm the strain-difference in response to TBDD treatment, cytochrome P450 (CYP) 1A1 and 1A2 protein levels were measured in both strains. A dose of 10 µg/kg body weight of TBDD induced hepatic CYP1A1 and CYP1A2 expression in both strains, but the expression levels of both CYP1A proteins were higher in C3H/lpr mice than in MRL/lpr mice, supporting that C3H/lpr mice are more sensitive to dioxins than MRL/lpr mice. Proteins that were more induced or suppressed by TBDD treatment in C3H/lpr mice were successfully identified by 2-DE and MALDI-TOF/TOF, including proteins responsible for AHR activation through production of endogenous ligands such as aspartate aminotransferase, indolethylamine N-methyltransferase, and aldehyde dehydrogenases, as well as proteins reducing oxidative stress, such as superoxide dismutase and peroxiredoxins. Taken together, our results provide insights into the molecular mechanism underlying the high dioxin susceptibility of the C3H/lpr strain, in which AHR activation by TBDD is more prompted by the production of endogenous ligands, but the adaptation to oxidative stress is also acquired.
Laboratory of Environmental Toxicology, Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, 790-8577, Japan.
Hoa Thanh
HT
Nguyen
Laboratory of Environmental Toxicology, Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, 790-8577, Japan.|Institute of Biological Sciences, University of the Philippines Los Baños, Laguna, Philippines.
Maria Claret Lauan
MC
Tsuchiya
Laboratory of Environmental Toxicology, Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, 790-8577, Japan.
Jean
J
Yoo
Graduate School of Computer Science and System Engineering, Kyushu Institute of Technology, Iizuka, 820-0067, Japan.
Midori
M
Iida
Laboratory of Environmental Toxicology, Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, 790-8577, Japan.|Graduate School of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto, 862-8502, Japan.
Tetsuro
T
Agusa
Laboratory of Environmental Toxicology, Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, 790-8577, Japan.
Masashi
M
Hirano
Department of Life and Nanopharmaceutical Science and Department of Biology, Kyung Hee University, Seoul, 130-701, Korea.
Eun-Young
EY
Kim
Gifu University Hospital, Gifu, 501-1194, Japan.
Tatsuhiko
T
Miyazaki
Institute for Promotion of Advanced Science and Technology, Ehime University, Matsuyama, 790-8577, Japan.
Masato
M
Nose
Laboratory of Environmental Toxicology, Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, 790-8577, Japan. iwatah@agr.ehime-u.ac.jp.
Hisato
H
Iwata
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004147:Dioxins / Q000633:toxicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D018384:Oxidative Stress / Q000187:drug effects*; D020543:Proteome / Q000187:drug effects; D040901:Proteomics / Q000379:methods; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D004147:Dioxins; D020543:Proteome; D018336:Receptors, Aryl Hydrocarbon; C066841:2,3,7,8-tetrabromodibenzo-4-dioxin; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2
C3H/lpr; Dioxin; MRL/lpr; Proteome; Susceptibility