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

University of Rochester Medical Center, Environmental Medicine, Rochester, New York 14642, USA .
Thrombosis and Haemostasis (Impact Factor: 5.76). 02/2008; 99(1):86-95. DOI: 10.1160/TH07-05-0328
Source: PubMed

ABSTRACT Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPARgamma and that PPARgamma ligands blunt platelet activation. To further understand the nature of PPARgamma in platelets, we determined the platelet PPARgamma isoform(s) and investigated the fate of PPARgamma following platelet activation. Our studies demonstrated that human platelets contain only the PPARgamma1 isoform and after activation with thrombin, TRAP, ADP or collagen PPARgamma is released from internal stores. PPARgamma release was blocked by a cytoskeleton inhibitor, Latrunculin A. Platelet-released PPARgamma was complexed with the retinoid X receptor (RXR) and retained its ability to bind DNA. Interestingly, the released PPARgamma and RXR were microparticle associated and the released PPARgamma/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 PPARgamma 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 PPARgamma has an undiscovered role in human biology.

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Available from: Neil Blumberg, Feb 10, 2014
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    • "Megakaryocytes and platelets express PPARγ (Akbiyik et al., 2004), and recently we reported that PPARγ1 is released from activated platelets and in platelet microparticles as an active transcription factor complex with RXR (Ray et al., 2008). Internalization of PPARγcontaining platelet microparticles elicits a transcellular attenuation of THP-1 monocytic cell activation in the presence of the PPARγ agonist, rosiglitazone (Ray et al., 2008). PPARγ activation exerts anti-inflammatory effects in nucleated cells via nongenomic mechanisms (Ray et al., 2006). "
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