Proteomics for the discovery of nuclear bile acid receptor FXR targets

Cissi Gardmo, Antonio Tamburro, Salvatore Modica, Antonio Moschetta

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)836-841
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1812
Issue number8
DOIs
StatePublished - Aug 2011

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Cytoplasmic and Nuclear Receptors
Bile Acids and Salts
Proteomics
Proteins
Liver
Two-Dimensional Difference Gel Electrophoresis
Ligands
Mitochondrial Proteins
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
MicroRNAs
Lipid Metabolism
Homeostasis
Transcription Factors
Cholesterol
Pharmacology
Glucose
Messenger RNA
Health
Neoplasms

Keywords

  • Expression profiling
  • FXR
  • Mitochondrial
  • Nuclear receptor
  • Post-transcriptional modification
  • Proteomic analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Proteomics for the discovery of nuclear bile acid receptor FXR targets. / Gardmo, Cissi; Tamburro, Antonio; Modica, Salvatore; Moschetta, Antonio.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1812, No. 8, 08.2011, p. 836-841.

Research output: Contribution to journalArticle

Gardmo, Cissi ; Tamburro, Antonio ; Modica, Salvatore ; Moschetta, Antonio. / Proteomics for the discovery of nuclear bile acid receptor FXR targets. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2011 ; Vol. 1812, No. 8. pp. 836-841.
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