| Oxidative metabolism of linoleic acid modulates PPAR-beta/delta suppression of PPAR-gamma activity. | |
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MedLine Citation:
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PMID: 16288226 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peroxisome proliferator-activated receptors (PPARs) are transcription factors that strongly influence molecular events in normal and cancer cells. PPAR-beta/delta (PPAR-b/d) overexpression suppresses the activity of PPAR-gamma (PPAR-g) and PPAR-alpha. This interaction has been questioned, however, by studies with synthetic ligands of PPARs in PPAR-b/d-null cells, and it is not known whether an interaction between PPAR-b/d and PPAR-g exists, especially in relation to the signaling by natural PPAR ligands. Oxidative metabolites of linoleic and arachidonic acids are natural ligands of PPARs. 13-S-hydroxyoctadecadienoic acid (13-S-HODE), the main product of 15-lipoxygenase-1 (15-LOX-1) metabolism of linoleic acid, downregulates PPAR-b/d. We tested (a) whether PPAR-b/d expression modulates PPAR-g activity in experimental models of the loss and gain of PPAR-b/d function in colon cancer cells and (b) whether 15-LOX-1 formation of 13-S-HODE influences the interaction between PPAR-b/d and PPAR-g. We found that (a) 15-LOX-1 formation of 13-S-HODE promoted PPAR-g activity, (b) PPAR-b/d expression suppressed PPAR-g activity in models of both loss and gain of PPAR-b/d function, (c) 15-LOX-1 activated PPAR-g by downregulating PPAR-b/d, and (d) 15-LOX-1 expression induced apoptosis in colon cancer cells via modulating PPAR-b/d suppression of PPAR-g. These findings elucidate a novel mechanism of the signaling by natural ligands of PPARs, which involves modulating the interaction between PPAR-b/d and PPAR-g. |
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Authors:
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X Zuo; Y Wu; J S Morris; J B Stimmel; L M Leesnitzer; S M Fischer; S M Lippman; I Shureiqi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 25 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-02-23 Completed Date: 2006-03-28 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 1225-41 Citation Subset: IM |
Copyright Information:
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Oncogene (2006) 25, 1225-1241. doi:10.1038/sj.onc.1209160; published online 14 November 2005. |
Affiliation:
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Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1439, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Arachidonate 15-Lipoxygenase / metabolism Colorectal Neoplasms / drug therapy*, metabolism Down-Regulation Humans Linoleic Acid / pharmacology* Linoleic Acids / metabolism Oxidation-Reduction PPAR delta / antagonists & inhibitors, metabolism* PPAR gamma / antagonists & inhibitors, metabolism* PPAR-beta / antagonists & inhibitors, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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ES07784/ES/NIEHS NIH HHS; R01 CA104278/CA/NCI NIH HHS; R01 CA104278-01A1/CA/NCI NIH HHS; R01 CA104278-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Linoleic Acids; 0/PPAR delta; 0/PPAR gamma; 0/PPAR-beta; 2197-37-7/Linoleic Acid; 5204-88-6/13-hydroxy-9,11-octadecadienoic acid; EC 1.13.11.33/Arachidonate 15-Lipoxygenase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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