liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Differential recruitment of the coactivator proteins CREB-binding protein and steroid receptor coactivator-1 to peroxisome proliferator-activated receptor gamma/9-cis-retinoic acid receptor heterodimers by ligands present in oxidized low-density lipoprotein
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
University of California, San Diego, La Jolla, CA, USA.
Show others and affiliations
2003 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 0022-0795, Vol. 177, no 2, 207-214 p.Article in journal (Refereed) Published
Abstract [en]

Peroxisome proliferator-activated receptor gamma (PPAR?) colocalizes with oxidized low-density lipoprotein (LDL) in foam cells in atherosclerotic lesions. We have explored a potential role of oxidized fatty acids in LDL as PPAR? activators. LDL from patients suffering from intermittent claudication due to atherosclerosis was analyzed using HPLC and gas chromatography/mass spectrophotometry and found to contain 9-hydroxy-and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), as well as 5-hydroxy-, 12-hydroxy- and 15-hydroxyeicosatetraenoic acid (5-, 12- and 15-HETE respectively). PPAR? was potently activated by 13(S)-HODE and 15(S)-HETE, as judged by transient transfection assays in macrophages or CV-1 cells. 5(S)- and 12(S)-HETE as well as 15-deoxy-?12,14 -prostaglandin J2 also activated PPAR? but were less potent. Interestingly, the effect of the lipoxygenase products 13(S -HODE and 15(S)-HETE as well as of the drug rosiglitazone were preferentially enhanced by the coactivator CREB-binding protein, whereas the effect of the cyclooxygenase product 15-deoxy-?12,14-prostaglandin J2 was preferentially enhanced by steroid receptor coactivator-1. We interpret these results, which may have relevance to the pathogenesis of atherosclerosis, to indicate that the lipoxygenase products on the one hand and the cyclooxygenase product on the other exert specific effects on the transcription of target genes through differential coactivator recruitment by PPAR?/9-cis retinoic acid receptor heterodimer complexes.

Place, publisher, year, edition, pages
2003. Vol. 177, no 2, 207-214 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-25057DOI: 10.1677/joe.0.1770207ISI: 000183063900003PubMedID: 12740008Local ID: 9485OAI: diva2:245383
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2013-10-22

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Wigren, JaneOlsson, AndersHammarström, SvenSöderström, Mats
By organisation
Cell biologyFaculty of Health SciencesInternal MedicineEMT-endo
In the same journal
Journal of Endocrinology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 54 hits
ReferencesLink to record
Permanent link

Direct link