Diabetes has been reported to increase CYP2E1 (cytochrome P450) and CYP2B1 expression at both the mRNA and protein levels in rat livers. This increase has been attributed to mRNA stabilization and can be reversed by daily insulin treatment. In a previous study, we showed that this hormone directly down-regulates CYP2E1 and 2B1 expression through a post-transcriptional mechanism in rat hepatoma cell lines. We then aimed to identify the molecular mechanisms involved in this regulation. We first identified a 16-mer sequence that we later showed to be the actual functional target of insulin on the rat CYP2E1 mRNA. Similar work was performed with CYP2B1. We first investigated the presence of mRNA–protein interactions. Using cytoplasmic proteins of Fao cells treated or not with insulin (0.1 μM) and the full-length CYP2B1 mRNA as a probe, a major CYP2B1 RNA–protein complex was observed with RNase T1 protection experiments. With the use of different CYP2B1 mRNA probes and by means of competition experiments with antisense oligonucleotides, a protein fixation site was located on a 16-nt sequence in the 5′ part of the coding region. This sequence has a hairpin loop structure, shows 80% sequence identity with a structure previously identified on CYP2E1 and is also responsible for the post-transcriptional effects of insulin on this mRNA. Protein(s) bound to both CYP2B1 and CYP2E1 sequences are cytosolic and have an apparent molecular mass of 60 kDa. The protein(s) that bind(s) to both these sequences and the insulin transduction signal involved in this regulation remain(s) to identified.
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Research Article|
May 10 2005
Regulatory sequence responsible for insulin destabilization of cytochrome P450 2B1 (CYP2B1) mRNA
Nhu-Traï TRUONG;
Nhu-Traï TRUONG
1INSERM UMR-S490, Laboratoire de Toxicologie Moléculaire, Faculté de Médecine, 45 Rue des Saints Pères 75270, Paris Cedex 06, France
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Arlette MONCION;
Arlette MONCION
1INSERM UMR-S490, Laboratoire de Toxicologie Moléculaire, Faculté de Médecine, 45 Rue des Saints Pères 75270, Paris Cedex 06, France
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Robert BAROUKI;
Robert BAROUKI
1INSERM UMR-S490, Laboratoire de Toxicologie Moléculaire, Faculté de Médecine, 45 Rue des Saints Pères 75270, Paris Cedex 06, France
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Philippe BEAUNE;
Philippe BEAUNE
1INSERM UMR-S490, Laboratoire de Toxicologie Moléculaire, Faculté de Médecine, 45 Rue des Saints Pères 75270, Paris Cedex 06, France
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Isabelle de WAZIERS
Isabelle de WAZIERS
1
1INSERM UMR-S490, Laboratoire de Toxicologie Moléculaire, Faculté de Médecine, 45 Rue des Saints Pères 75270, Paris Cedex 06, France
1To whom correspondence should be addressed (email Isabelle.Waziers@univ-paris5.fr).
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Publisher: Portland Press Ltd
Received:
September 03 2004
Revision Received:
December 10 2004
Accepted:
December 23 2004
Accepted Manuscript online:
December 23 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 388 (1): 227–235.
Article history
Received:
September 03 2004
Revision Received:
December 10 2004
Accepted:
December 23 2004
Accepted Manuscript online:
December 23 2004
Citation
Nhu-Traï TRUONG, Arlette MONCION, Robert BAROUKI, Philippe BEAUNE, Isabelle de WAZIERS; Regulatory sequence responsible for insulin destabilization of cytochrome P450 2B1 (CYP2B1) mRNA. Biochem J 15 May 2005; 388 (1): 227–235. doi: https://doi.org/10.1042/BJ20041510
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