The nuclear bile acid receptor FXR as a novel therapeutic target in cholestatic liver diseases: Hype or hope?

Michael Trauner – 30 June 2004 – Farnesoid X receptor (FXR) is a bile acid–activated transcription factor that is a member of the nuclear hormone receptor superfamily. FXR‐null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis.

Characterization of mutations in ATP8B1 associated with hereditary cholestasis

Leo W. J. Klomp, Julie C. Vargas, Saskia W. C. van Mil, Ludmila Pawlikowska, Sandra S. Strautnieks, Michiel J. T. van Eijk, Jenneke A. Juijn, Carlos Pabón‐Peña, Lauren B. Smith, Joseph A. DeYoung, Jane A. Byrne, Justijn Gombert, Gerda van der Brugge, Ruud Berger, Irena Jankowska, Joanna Pawlowska, Erica Villa, A. S. Knisely, Richard J. Thompson, Nelson B. Freimer, Roderick H. J. Houwen, Laura N. Bull – 30 June 2004 – Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders.

Mitochondrial nitric oxide synthase drives redox signals for proliferation and quiescence in rat liver development

María C. Carreras, Daniela P. Converso, Alicia S. Lorenti, Mariana Barbich, Damián M. Levisman, Ariel Jaitovich, Valeria G. Antico Arciuch, Soledad Galli, Juan J. Poderoso – 30 June 2004 – Mitochondrial nitric oxide synthase (mtNOS) is a fine regulator of oxygen uptake and reactive oxygen species that eventually modulates the activity of regulatory proteins and cell cycle progression.

Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source

Susan M. McKiernan, Richard Hagan, Michael Curry, George S. A. McDonald, Alan Kelly, Niamh Nolan, Anne Walsh, John Hegarty, Emer Lawlor, Dermot Kelleher – 30 June 2004 – The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome.

S‐adenosylmethionine and its metabolite induce apoptosis in HepG2 cells: Role of protein phosphatase 1 and Bcl‐xS

Heping Yang, Mamatha R. Sadda, Mei Li, Ying Zeng, Lixin Chen, Wanjun Bae, Xiaopeng Ou, Maria T. Runnegar, José M. Mato, Shelly C. Lu – 30 June 2004 – S‐adenosylmethionine (SAMe) and its metabolite 5′‐methylthioadenosine (MTA) are proapoptotic in HepG2 cells. In microarray studies, we found SAMe treatment induced Bcl‐x expression. Bcl‐x is alternatively spliced to produce two distinct mRNAs and proteins, Bcl‐xL and Bcl‐xS. Bcl‐xL is antiapoptotic, while Bcl‐xS is proapoptotic.

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