PUBLICATION

Phenylthiourea as a weak activator of aryl hydrocarbon receptor inhibiting 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 transcription in zebrafish embryo

Authors
Wang, W.D., Wang, Y., Wen, H.J., Buhler, D.R., and Hu, C.H.
ID
ZDB-PUB-040609-11
Date
2004
Source
Biochemical pharmacology   68(1): 63-71 (Journal)
Registered Authors
Buhler, Donald R., Hu, Chin-Hwa
Keywords
Phenylthiourea (PTU), CYP1A1, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), Aryl hydrocarbon receptor 2 (AHR2), Aryl hydrocarbon receptor nuclear translocator (ARNT), Zebrafish PTU, phenylthiourea; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; CYP1A1, cytochrome P4501A1; AHR, aryl hydrocarbon receptor; ARNT, aryl hydrocarbon receptor nuclear translocator; hpf, hours post-fertilization
MeSH Terms
  • Animals
  • Cytochrome P-450 CYP1A1/genetics
  • Cytochrome P-450 CYP1A1/metabolism*
  • Drug Interactions
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/enzymology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation/drug effects
  • Phenylthiourea/pharmacology*
  • RNA, Messenger/drug effects
  • RNA, Messenger/metabolism
  • Receptors, Aryl Hydrocarbon/metabolism*
  • Signal Transduction/drug effects
  • Signal Transduction/physiology
  • Transcription, Genetic/drug effects*
  • Zebrafish
PubMed
15183118 Full text @ Biochem. Pharmacol.
CTD
15183118
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that can be activated by a diverse synthetic and naturally-occurring chemicals, such as the halogenated aromatic hydrocarbons (HAHs) and the non-halogenated polycyclic aromatic hydrocarbons (PAHs). The liganded AHR modulates the genetic activity of a variety of xenobiotic-responsive genes, including cytochrome P4501A1 (CYP1A1). The tyrosinase inhibitor 1-phenyl-2-thiourea (PTU) is widely used in zebrafish research to suppress pigmentation in developing embryos/fry. Here we showed that 0.2mM PTU induced a basal level of CYP1A1 transcription in zebrafish embryonic integument as early as 24h postfertilization (hpf) stage. Subsequently, PTU induced CYP1A1 transcription in blood vessels at 36hpf. During larval stage, the liver and all pharyngeal arch vessels of PTU-treated embryos exhibited CYP1A1 transcription as well. Comparing to TCDD, PTU induces CYP1A1 transcription with much lower efficacy in zebrafish embryos. Coincubating the embryos with PTU and TCDD led to repressing TCDD-induced CYP1A1 transcription. Mechanistic studies indicated that both of PTU- and TCDD-mediated CYP1A1 transcriptions are modulated by the same AHR-ARNTsignaling pathway.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping