Cholesterol 7α-hydroxylase, CYP7A1, is the rate-limiting enzyme in the conversion of cholesterol to bile acids (BA). Excretion of BA is mediated by the bile salt export pump, BSEP, CYP7A1 and BZEP expression is regulated by e negative feedback and positive feed-forward mechanism, respectively, through BA-mediated activation of farnesoid X receptor, FXR. Histone deacetylases, HDACs, and fibroblast growth factor 19, FGF19, play a key role in the regulation of CYP7A1 gene transcription. FGF19 signals from intestine to liver to repress CYP7A1 via a JNK-dependent pathway. The aim of this work is to characterize a cellular model to investigate the effect of HDACs silencing on cholesterol homeostasis. In human and murine hepatic cell cultures, siRNAs targeting specific HDACs and SMRT/N-CoR have been identified. In four hepatic cell lines, treated with BA and FGF19, gene expression of HDACs, CYP7A1, SHP and BSEP has been determined. Preliminary results suggest Hep3B as a possible cellular model for further investigations. (Funded by CARIPLO Foundation 2008.2511)

Characterization of a cellular model for studing the effect of HDACs silencing on cholesterol homeostasis / C. Multineddu, E. Fiorino, F. Gilardi, A. Galmozzi, M. Giudici, N. Mitro, E.S.R. De Fabiani, D. Caruso, M. Crestani. ((Intervento presentato al 55. convegno National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) tenutosi a Milano nel 2010.

Characterization of a cellular model for studing the effect of HDACs silencing on cholesterol homeostasis

C. Multineddu;E. Fiorino;F. Gilardi;A. Galmozzi;M. Giudici;N. Mitro;E.S.R. De Fabiani;D. Caruso;M. Crestani
2010-09-14

Abstract

Cholesterol 7α-hydroxylase, CYP7A1, is the rate-limiting enzyme in the conversion of cholesterol to bile acids (BA). Excretion of BA is mediated by the bile salt export pump, BSEP, CYP7A1 and BZEP expression is regulated by e negative feedback and positive feed-forward mechanism, respectively, through BA-mediated activation of farnesoid X receptor, FXR. Histone deacetylases, HDACs, and fibroblast growth factor 19, FGF19, play a key role in the regulation of CYP7A1 gene transcription. FGF19 signals from intestine to liver to repress CYP7A1 via a JNK-dependent pathway. The aim of this work is to characterize a cellular model to investigate the effect of HDACs silencing on cholesterol homeostasis. In human and murine hepatic cell cultures, siRNAs targeting specific HDACs and SMRT/N-CoR have been identified. In four hepatic cell lines, treated with BA and FGF19, gene expression of HDACs, CYP7A1, SHP and BSEP has been determined. Preliminary results suggest Hep3B as a possible cellular model for further investigations. (Funded by CARIPLO Foundation 2008.2511)
Settore BIO/10 - Biochimica
http://www.biochimica.it/congressiecorsi.html
Characterization of a cellular model for studing the effect of HDACs silencing on cholesterol homeostasis / C. Multineddu, E. Fiorino, F. Gilardi, A. Galmozzi, M. Giudici, N. Mitro, E.S.R. De Fabiani, D. Caruso, M. Crestani. ((Intervento presentato al 55. convegno National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) tenutosi a Milano nel 2010.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/164830
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