Proteomics for the discovery of nuclear bile acid receptor FXR targets

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Review

Gardmo, Cissi¹  Moschetta, Antonio² 

[1] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Lab Lipid Metab & Canc, Dept Translat Pharmacol, I-66030 Santa Maria Imbaro, CH, Italy

[2] Univ Bari, Dept Internal & Publ Med, Clin Med A Murri, I-70124 Bari, Italy

关键词: Nuclear receptor;    FXR;    Proteomic analysis;    Expression profiling;    Post-transcriptional modification;    Mitochondrial;   

DOI  :  10.1016/j.bbadis.2011.03.009

来源: Elsevier

【 摘 要 】

Nuclear receptors (NRs) are important pharmacological targets for a number of diseases, including cancer and metabolic disorders. To unmask the direct role of NR function it is fundamental to find the NR targets. During the last few years several NRs have been shown to affect microRNA expression, thereby modulating protein levels. The farnesoid X receptor (FXR), the main regulator of bile acid (BA) homeostasis, also regulates cholesterol, lipid and glucose metabolism. Here we used, for the first time, a proteomics approach on mice treated with a FXR ligand to find novel hepatic FXR targets. Nineteen spots with a more than two-fold difference in protein amounts were found by 2D-DIGE and 20 proteins were identified by MALDI-TOF MS as putative novel FXR targets. The most striking feature of the protein list was the great number of mitochondrial proteins, indicating a substantial impact of FXR activation on mitochondrial function in the liver. To examine if the differences found in the proteomics assay reflected differences at the mRNA level, a microarray assay was generated on hepatic samples from wild type and FXR(-/-) mice treated with a FXR ligand and compared to vehicle treatment. At least six proteins were shown to be regulated only at a post-transcriptional level. In conclusion, our study provides the impetus to include proteomic analysis for the identification of novel targets of transcription factors, such as NRs. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free