The Role of PPAR Ligands in Controlling Growth-Related Gene Expression and their Interaction with Lipoperoxidation Products

Author:

Barrera Giuseppina1ORCID,Toaldo Cristina1,Pizzimenti Stefania1,Cerbone Angelo2,Pettazzoni Piergiorgio1,Dianzani Mario Umberto1,Ferretti Carlo3

Affiliation:

1. Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Generale, Corso Raffaello 30, 10125 Torino, Italy

2. Istituto di Ricerche Biomediche “A. Marxer” RBM Merck Serono, Via Ribes 1, 10010 Colleretto Giacosa (Torino), Italy

3. Dipartimento di Anatomia, Farmacologia e Medicina Legale, sezione di Farmacologia, Via P. Giuria 13, 10125 Torino, Italy

Abstract

Peroxisome proliferators-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. The three PPAR isoforms (, and ) have been found to play a pleiotropic role in cell fat metabolism. Furthermore, in recent years, evidence has been found regarding the antiproliferative, proapoptotic, and differentiation-promoting activities displayed by PPAR ligands, particularly by PPAR ligands. PPAR ligands affect the expression of different growth-related genes through both PPAR-dependent and PPAR-independent mechanisms. Moreover, an interaction between PPAR ligands and other molecules which strengthen the effects of PPAR ligands has been described. Here we review the action of PPAR on the control of gene expression with particular regard to the effect of PPAR ligands on the expression of genes involved in the regulation of cell-cycle, differentiation, and apoptosis. Moreover, the interaction between PPAR ligands and 4-hydroxynonenal (HNE), the major product of the lipid peroxidation, has been reviewed.

Publisher

Hindawi Limited

Subject

Pharmacology (medical),Drug Discovery

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