Altmann, Reinhold and Hausmann, Martin and Spoettl, Tanja and Gruber, Michael and Bull, Arthur W. and Menzel, Katrin and Vogl, Daniela and Herfarth, Hans and Schoelmerich, Juergen and Falk, Werner and Rogler, Gerhard (2007) 13-oxo-ODE is an endogenous ligand for PPAR gamma in human colonic epithelial cells. BIOCHEMICAL PHARMACOLOGY, 74 (4). pp. 612-622. ISSN 0006-2952,
Full text not available from this repository. (Request a copy)Abstract
Background: The ligand activated nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) induces transcriptional repression of pro-inflammatory factors. Activation of PPAR-gamma is followed by amelioration of colitis in animal models of inflammatory bowel disease (IBD). A reduced expression of PPAR-gamma was found in epithelial cells of patients with ulcerative colitis. The eicosanoids 13-HODE and 15-HETE are products of 12/15-lipoxygenase (LOX) and endogenous ligands for PPAR gamma. Dehydrogenation of 13-HODE by 13-HODE dehydrogenase results in formation of the 13-Oxo-ODE. Highest activity of 13-HODE dehydrogenase is found in colonic epithelial cells (CECs). We therefore investigated whether 13-Oxo-ODE is a new endogenous ligand of PPAR gamma in CECs. Methods: LOX activity and 13-HODE dehydrogenase in CECs were investigated after stimulation with arachidonic or linoleic acid. LOX metabolites were identified by RP-18 reversed-phase HPLC. Binding of C-14-labelled 13-Oxo-ODE was demonstrated using a His-tagged PPAR gamma Results: Stimulation of HT-29 and primary CECs homogenates with and without Ca-ionophor was followed by the formation of high amounts of the linoleic acid metabolite 13-Oxo-ODE (155 and 8S ng/ml). The decrease of IL-8 secretion from IEC was more pronounced after pre-incubation with 13-Oxo-ODE compared to the PPAR gamma agonist troglitazone and higher as with the known PPAR gamma ligands 13-HODE and 15-HETE. Binding assays with C-14-labelled (13)Oxo-ODE clearly demonstrated a direct interaction.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED-RECEPTOR-GAMMA; INFLAMMATORY-BOWEL-DISEASE; ACID DEHYDROGENASE-ACTIVITY; MACROPHAGE GENE-EXPRESSION; NF-KAPPA-B; 13-HODE DEHYDROGENASE; LINOLEIC-ACID; ULCERATIVE-COLITIS; DIFFERENTIATION; PIOGLITAZONE; 13-oxo-ODE; endogenous ligand; 13-HODE dehydrogenase; Ulcerative colitis; PPAR gamma; colonic epithelial cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 14:03 |
| Last Modified: | 01 Dec 2020 14:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32385 |
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