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Title: Constitutive and xenobiotics-induced expression of a novel CYP3A gene from zebrafish larva

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [1];  [2];  [3];  [3]
  1. Department of Life Science, National Tsing-Hua University, Hsinchu, Taiwan (China)
  2. Department of Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States)
  3. Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan (China)

In mammals, CYP3A isozymes collectively comprise the largest portion of the liver and small intestinal CYP protein. They are involved in the metabolism of an extensive range of endogenous substrates and xenobiotics and make a significant contribution to the termination of the action of steroid hormones. A full-length cDNA of CYP3A gene, named CYP3A65, was cloned from zebrafish by RT-PCR. The CYP3A65 mRNA was initially transcribed only in the liver and intestine upon hatching of the zebrafish embryos. Like the human CYP3A genes, CYP3A65 transcription in the foregut region was enhanced by treatment of the zebrafish larvae with the steroid dexamethasone and the macrocyclic antibiotic rifampicin. Differing from mammalian CYP3A genes, CYP3A65 transcription was also elicited by 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) during early larval stages. Repression of AHR2 translation by antisense morpholino oligonucleotides abrogated both of constitutive and TCDD-stimulated CYP3A65 transcription in larval intestine. These findings suggested that the AHR2 signaling pathway plays an essential role in CYP3A65 transcription.

OSTI ID:
20721824
Journal Information:
Toxicology and Applied Pharmacology, Vol. 205, Issue 3; Other Information: DOI: 10.1016/j.taap.2004.10.019; PII: S0041-008X(04)00495-8; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
Country of Publication:
United States
Language:
English