Document Detail


Peroxisome proliferator-activated receptor gamma and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles.
MedLine Citation:
PMID:  18217139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Denise M Ray; Sherry L Spinelli; Stephen J Pollock; Thomas I Murant; Jamie J O'Brien; Neil Blumberg; Charles W Francis; Mark B Taubman; Richard P Phipps
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  99     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-02-21     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  86-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Bicyclo Compounds, Heterocyclic / pharmacology
Blood Platelets / drug effects,  metabolism*
Cell Line, Tumor
Collagen / metabolism
DNA / metabolism
Dimerization
Female
Humans
Male
Megakaryocytes / metabolism
Middle Aged
Monocytes / metabolism
PPAR gamma / agonists,  metabolism*
Peptide Fragments / metabolism
Platelet Activation*
Protein Binding
Protein Isoforms / metabolism
RNA, Messenger / metabolism
Retinoid X Receptor alpha / metabolism
Retinoid X Receptor beta / metabolism
Retinoid X Receptors / genetics,  metabolism*
Thiazolidinediones / pharmacology
Thiazolidines / pharmacology
Thrombin / metabolism
Time Factors
Transport Vesicles / metabolism*
Grant Support
ID/Acronym/Agency:
DE011390/DE/NIDCR NIH HHS; ES01247/ES/NIEHS NIH HHS; HL078603/HL/NHLBI NIH HHS; HL0786367/HL/NHLBI NIH HHS; P30 ES001247/ES/NIEHS NIH HHS; P30 ES001247-250109/ES/NIEHS NIH HHS; R01 DE011390/DE/NIDCR NIH HHS; R01 DE011390-19/DE/NIDCR NIH HHS; R01 HL078603/HL/NHLBI NIH HHS; R01 HL078603-03/HL/NHLBI NIH HHS; T32-DE07165/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Bicyclo Compounds, Heterocyclic; 0/PPAR gamma; 0/Peptide Fragments; 0/Protein Isoforms; 0/RNA, Messenger; 0/Retinoid X Receptor alpha; 0/Retinoid X Receptor beta; 0/Retinoid X Receptors; 0/Thiazolidinediones; 0/Thiazolidines; 0/thrombin receptor peptide (42-47); 122320-73-4/rosiglitazone; 76343-93-6/latrunculin A; 9007-34-5/Collagen; 9007-49-2/DNA; EC 3.4.21.5/Thrombin
Comments/Corrections

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