Advertisement
Advertisement

Contact Person

Dr. Elinor Switzer

Managing Editor

Phone: +49 (0)711 - 2 29 87 63
Fax: +49 (0)711 - 2 29 87 65
send an Email


Archive

Peroxisome proliferator-activated receptor γ and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH07-05-0328
Issue: 2008: 99/1 (Jan) pp. 1-248
Pages: 86-95

Peroxisome proliferator-activated receptor γ and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles

Denise M. Ray*1, Sherry L. Spinelli*2, Stephen J. Pollock1, Thomas I. Murant1, Jamie J. O’Brien1, Neil Blumberg2, Charles W. Francis3, Mark B. Taubman4, Richard P. Phipps1
University of Rochester Medical Center, 1Environmental Medicine; 2Pathology and Laboratory Medicine; 3Medicine: Hematology-Oncology; 4Center for Cellular and Molecular Cardiology, Rochester, New York, USA

Keywords

Platelets, microparticles, transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), retinoic X receptor (RXR)

Summary

Peroxisome proliferator-activated receptor γ (PPARγ) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPARγ and that PPARγ ligands blunt platelet activation. To further understand the nature of PPARγ in platelets, we determined the platelet PPARγ isoform(s) and investigated the fate of PPARγ following platelet activation. Our studies demonstrated that human platelets contain only the PPARγ1 isoform and after activation with thrombin,TRAP,ADP or collagen PPARγ is released from internal stores. PPARγ release was blocked by a cytoskeleton inhibitor, Latrunculin A. Platelet-released PPARγ was complexed with the retinoid X receptor (RXR) and retained its ability to bind DNA. Interestingly, the released PPARγ and RXR were microparticle associated and the released PPARγ/RXR complex retained DNA-binding ability.Additionally, a monocytic cell line,THP-1, is capable of internalizing PMPs. Further investigation following treatment of these cells with the PPARγ agonist, rosiglitazone and PMPs revealed a possible transcellular mechanism to attenuate THP-1 activation. These new findings are the first to demonstrate transcription factor release from platelets, revealing the complex spectrum of proteins expressed and expelled from platelets,and suggests that platelet PPARγ has an undiscovered role in human biology.

You may also be interested in...

1.
C. Reinhardt

Hämostaseologie 2007 27 1: 55-58

2.
Gregor Hron1, Marietta Kollars1, Heinz Weber1, Verena Sagaster1, Peter Quehenberger2, Sabine Eichinger1, Paul A. Kyrle1, Ansgar Weltermann1

Thromb Haemost 2007 97 1: 119-123

http://dx.doi.org/10.1160/TH06-03-0141

3.

M. P. G. Leers (1), J. F. W. Keuren (2, 3), M. E. P. W. Frissen (1), M. Huts (1), J. A. Kragten (4), K.-S. G. Jie (5)

Thromb Haemost 2013 110 1: 101-109

http://dx.doi.org/10.1160/TH12-09-0643