The 4S benzo(a)pyrene-binding protein is not a transcriptional activator of Cyp1a1 gene in Ah receptor-deficient (AHR -/-) transgenic mice

Archives of Biochemistry and Biophysics
J FoussatP Lesca

Abstract

In an effort to better understand the role of the 4S benzo(a)pyrene-binding protein in the induction of CYP1A1 by PAHs, we used a genetically engineered mouse line deficient in Ah receptor (AHR -/-). First, we demonstrated through binding experiments analyzed by sucrose gradient sedimentation and gel permeation chromatography that AHR -/- mice have no detectable AHR protein. In contrast, this AHR-deficient line expressed a 4S protein which efficiently binds BP as it does in hepatic cytosol from C57BL/6 mice. In vivo BP exposure in AHR-deficient mice proved the inability to sustain any CYP1A1 mRNA or CYP1A1 protein induction. These findings demonstrate the requirement of an active AHR to sustain the transactivation pathway leading to CYP1A1 induction. Surprisingly, the 4S BP-binding protein, which was previously characterized as the glycine N-methyltransferase, was completely devoid of such an enzymatic activity after purification by Sephacryl gel permeation chromatography. Moreover, sedimentation and chromatographic experiments, under nondenaturing conditions, do not support the assumption of 4S protein as a subunit of a multimeric protein (GNMT) displaying a molecular mass of 150 kDa.

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Citations

Oct 4, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jeanine A HarriganJames R Olson
Nov 14, 2012·Toxicology and Applied Pharmacology·Chia-Hung YenYi-Ming Arthur Chen
Nov 24, 2011·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Deacqunita L DiggsAramandla Ramesh

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