PMID: 11901218Mar 20, 2002Paper

Heterogeneous nuclear ribonucleoprotein A1 and regulation of the xenobiotic-inducible gene Cyp2a5

Molecular Pharmacology
Françoise Raffalli-MathieuM A Lang

Abstract

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) functions in the packaging of nascent RNA polymerase II transcripts and participates in a variety of nuclear and cytoplasmic processes that modulate gene expression. The RNA binding characteristics of hnRNP A1 suggest that it can modulate the expression of specific genes, but little is known about its possible targets in vivo. In this article, we show that hnRNP A1 interacts with the transcript of a cytochrome P450 gene, Cyp2a5, induced by xenobiotics and during liver damage. Binding of the hnRNP A1 to CYP2A5 mRNA was demonstrated by immunoprecipitation of the xenobiotic-stimulated (37/39 kDa) CYP2A5 mRNA-protein complex with a monoclonal anti-hnRNP A1 antibody, by partial trypsin digestion of the complex, and by showing that the RNA-protein complex is not formed with protein extracts from cells lacking the hnRNP A1. We also show that a specific hepatotoxic inducer of the Cyp2a5 gene, pyrazole, increases the cytoplasmic levels of hnRNP A1 in vivo. Finally, we show that hnRNP A1 can be overexpressed in mouse primary hepatocytes, leading to an accumulation of the CYP2A5 mRNA. Collectively, these results indicate that the hnRNP A1 is an important regulator of the Cyp2a5 gene.

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Citations

Jul 12, 2008·Archives of Toxicology·Olavi PelkonenHannu Raunio
Sep 3, 2008·Analytical and Bioanalytical Chemistry·Christina U Köhler, Peter H Roos
Sep 15, 2004·Toxicology and Applied Pharmacology·Ting Su, Xinxin Ding
Dec 18, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anke Van SummerenEdwin C M Mariman
May 1, 2013·Toxicology and Applied Pharmacology·Sangsoo Daniel KimGordon M Kirby
May 1, 2010·Expert Opinion on Drug Discovery·Masashi HonmaHiroshi Suzuki
Jul 14, 2012·Systems Biology in Reproductive Medicine·Sophie ChocuCharles Pineau
Jun 11, 2003·European Journal of Clinical Investigation·M LindellM A Lang
Apr 11, 2006·Genesis : the Journal of Genetics and Development·Dagmar WilhelmPeter Koopman
Aug 22, 2006·European Journal of Clinical Investigation·U S H SimonssonM A Lang
Feb 9, 2005·Chemico-biological Interactions·Hannu RaunioOlavi Pelkonen
May 12, 2004·Chemico-biological Interactions·Guoyu LingXinxin Ding
Dec 28, 2005·Biochemical and Biophysical Research Communications·Jue WangMagnus Ingelman-Sundberg
May 20, 2003·Biochemical Pharmacology·Tina GlisovicFrançoise Raffalli-Mathieu
May 23, 2018·Basic & Clinical Pharmacology & Toxicology·A'edah Abu-BakarMatti A Lang
May 8, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Noriaki SakaiMayumi Ishizuka
Nov 12, 2003·The Journal of Pharmacology and Experimental Therapeutics·W James Gilmore, Gordon M Kirby
Mar 22, 2014·Molecular and Clinical Oncology·Lin YangSongnian Hu
Mar 17, 2017·BMC Research Notes·Katia S PoçaAna C A X De-Oliveira

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