HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2007-0532v1 26/1/64    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sharifpanah, F. Articles by Sauer, H. Search for Related Content PubMed PubMed Citation Articles by Sharifpanah, F. Articles by Sauer, H.

EMBRYONIC STEM CELLS

Peroxisome Proliferator-Activated Receptor Agonists Enhance Cardiomyogenesis of Mouse ES Cells by Utilization of a Reactive Oxygen Species-Dependent Mechanism

^aDepartment of Physiology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany;
^bDepartment of Internal Medicine I, Cardiology Division, Friedrich-Schiller-University, Jena, Germany

Key Words. Embryonic stem cells • Peroxisome proliferator-activated receptor • heart • Cardiomyogenesis • Reactive oxygen species

Correspondence: Heinrich Sauer, M.D., Department of Physiology, Justus-Liebig-University Giessen, Aulweg 129, 35392 Giessen, Germany. Telephone: +49-641-9947333; Fax: +49-641-9947219; e-mail: heinrich.sauer{at}physiologie.med.uni-giessen.de

Received July 6, 2007; accepted for publication October 9, 2007.
First published online in STEM CELLS EXPRESS   October 18, 2007.



Peroxisome proliferator-activated receptors (PPAR, -β and -) are nuclear receptors involved in transcriptional regulation of lipid and energy metabolism. Since the energy demand increases when cardiac progenitor cells are developing rhythmic contractile activity, PPAR activation may play a critical role during cardiomyogenesis of embryonic stem (ES) cells. It is shown that ES cells express PPAR, -β, and - mRNA during differentiation of ES cells towards cardiac cells. Treatment with PPAR agonists (WY14643, GW7647, and ciprofibrate) significantly increased cardiomyogenesis and expression of the cardiac genes MLC2a, ANP, MHC-β, MLC2v, and cardiac -actin. Furthermore, WY14643 increased PPAR gene expression and the expression of the cardiogenic transcription factors GATA-4, Nkx2.5, DTEF-1, and MEF 2C. In contrast, the PPAR antagonist MK886 decreased cardiomyogenesis, whereas the PPARβ agonist L-165,041 as well as the PPAR agonist GW1929 were without effects. Treatment with PPAR, but not PPARβ, and PPAR agonists and MK886, resulted in generation of reactive oxygen species (ROS), which was inhibited in the presence of the NADPH oxidase inhibitors diphenylen iodonium (DPI) and apocynin and the free radical scavengers vitamin E and N-(2-mercapto-propionyl)-glycine (NMPG), whereas the mitochondrial complex I inhibitor rotenone was without effects. The effect of PPAR agonists on cardiomyogenesis of ES cells was abolished upon preincubation with free radical scavengers and NADPH oxidase inhibitors, indicating involvement of ROS in PPAR, mediated cardiac differentiation. In summary, our data indicate that stimulation of PPAR but not PPARβ and - enhances cardiomyogenesis in ES cells using a pathway that involves ROS and NADPH oxidase activity.

Disclosure of potential conflicts of interest is found at the end of this article.