PMID- 24858342
OWN - NLM
STAT- MEDLINE
DCOM- 20140923
LR  - 20181202
IS  - 1879-1514 (Electronic)
IS  - 0166-445X (Linking)
VI  - 154
DP  - 2014 Sep
TI  - Transient suppression of AHR activity in early red seabream embryos does not 
      prevent the disruption of peripheral nerve projection by 
      2,3,7,8-tetrachlorodibenzo-p-dioxin.
PG  - 39-47
LID - S0166-445X(14)00160-X [pii]
LID - 10.1016/j.aquatox.2014.05.001 [doi]
AB  - The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is 
      mainly mediated by an aryl hydrocarbon receptor (AHR), which regulates the 
      transcription of multiple target genes including cytochrome P450 1A (CYP1A). Our 
      pervious study identified the presence of TCDD-induced defects of peripheral 
      nerve projection in red seabream (Pagrus major) embryos. However, it remains 
      unclear whether the TCDD-induced peripheral neurotoxicity is mediated by the AHR. 
      To assess the contribution of the red seabream AHR (rsAHR) signaling pathway to 
      the neuronal toxicity, red seabream embryos at 10h post-fertilization (hpf) were 
      treated for 80 min with TCDD (0, 0.3, 5.3, and 37 nM in seawater) alone or in 
      combination with CH223191 (500 nM in seawater), which is an AHR antagonist. A 
      preliminary in vitro reporter gene assay confirmed that TCDD-induced 
      transcriptional activity via rsAHR1 and rsAHR2 was suppressed by CH223191 
      treatment in a dose-dependent manner. CYP1A mRNA expression in embryos was 
      determined by 2-step real time quantitative-polymerase chain reaction at 24 and 
      120 hpf and in situ hybridization at 48, 72, 96 and 120 hpf. The morphology of 
      the peripheral nerve system (PNS) was also microscopically observed by 
      fluorescent staining using an anti-acetylated tubulin antibody at 120 hpf. CYP1A 
      mRNA expression was dose-dependently induced by TCDD at all of the examined 
      developing stages. The suppression of TCDD-induced CYP1A expression by CH223191 
      treatment was observed in embryos at 24 and 48 hpf, while the effect of the rsAHR 
      antagonist disappeared at 96 and 120 hpf. This phenomenon indicated the transient 
      suppression of TCDD-induced rsAHR activation by CH223191 treatment. The 
      immunostaining of peripheral nerves at 120 hpf demonstrated that the projections 
      of the craniofacial nerve were altered in TCDD-treated embryos, and the frequency 
      of TCDD-induced abnormal projections was not prevented by co-treatment with 
      CH223191. These results indicate that the transient suppression of TCDD-induced 
      rsAHR activation during the early developing stages of the red seabream does not 
      influence the abnormal projection of peripheral nerves. In conclusion, transient 
      rsAHR activation in the early stages of development is not involved in the 
      neurotoxicity.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Iida, Midori
AU  - Iida M
AD  - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, 
      Matsuyama 790-8577, Japan.
FAU - Bak, Su-Min
AU  - Bak SM
AD  - Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 
      130-701, Republic of Korea; Department of Biology, Kyung Hee University, Seoul 
      130-701, Republic of Korea.
FAU - Murakami, Yasunori
AU  - Murakami Y
AD  - Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, 
      Japan.
FAU - Kim, Eun-Young
AU  - Kim EY
AD  - Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 
      130-701, Republic of Korea; Department of Biology, Kyung Hee University, Seoul 
      130-701, Republic of Korea.
FAU - Iwata, Hisato
AU  - Iwata H
AD  - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, 
      Matsuyama 790-8577, Japan. Electronic address: iwatah@agr.ehime-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140510
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide)
RN  - 0 (Azo Compounds)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Water Pollutants, Chemical)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Animals
MH  - Azo Compounds/pharmacology
MH  - Cytochrome P-450 CYP1A1/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Peripheral Nervous System/*drug effects
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Protein Binding/drug effects
MH  - Pyrazoles/pharmacology
MH  - Receptors, Aryl Hydrocarbon/*antagonists & inhibitors/*metabolism
MH  - Sea Bream/*embryology/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Water Pollutants, Chemical/*toxicity
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor
OT  - CH223191
OT  - Neurotoxicity
OT  - Red seabream
OT  - TCDD
EDAT- 2014/05/27 06:00
MHDA- 2014/09/24 06:00
CRDT- 2014/05/27 06:00
PHST- 2014/03/04 00:00 [received]
PHST- 2014/05/01 00:00 [revised]
PHST- 2014/05/02 00:00 [accepted]
PHST- 2014/05/27 06:00 [entrez]
PHST- 2014/05/27 06:00 [pubmed]
PHST- 2014/09/24 06:00 [medline]
AID - S0166-445X(14)00160-X [pii]
AID - 10.1016/j.aquatox.2014.05.001 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2014 Sep;154:39-47. doi: 10.1016/j.aquatox.2014.05.001. Epub 2014 
      May 10.