Journal Article

Activation of PPAR γ in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR γ

Arthur W. Bull, Knut R. Steffensen, Jörg Leers and Joseph J. Rafter

in Carcinogenesis

Volume 24, issue 11, pages 1717-1722
Published in print November 2003 | ISSN: 0143-3334
Published online November 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg131
Activation of PPAR γ in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR γ

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) γ plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for γ1, γ2 and γ3, in Caco-2 and HCT-116 colon cell lines showed that γ3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR γ by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR γ1 or γ2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR γ and that PPAR γ plays an important role in the differentiation of intestinal cells.

Keywords: 13-HODE, 13-hydroxyoctadecadienoic acid; 13-OXO, 13-oxooctadecadienoic acid; PPAR, peroxisome proliferator-activated receptor

Journal Article.  4927 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.