scholarly journals Derivation of a Retinoid X Receptor Scaffold from Peroxisome Proliferator-Activated Receptor γ Ligand 1-Di(1H-indol-3-yl)methyl-4-trifluoromethylbenzene

ChemMedChem ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. 1106-1119 ◽  
Author(s):  
Marcia I. Dawson ◽  
Mao Ye ◽  
Xihua Cao ◽  
Lulu Farhana ◽  
Qiong-Ying Hu ◽  
...  
Keyword(s):  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Peroxisome proliferator-activated receptor α-retinoid X receptor agonists induce beta-cell protection against palmitate toxicity

FEBS Journal ◽  
2007 ◽  
Vol 274 (23) ◽  
pp. 6094-6105 ◽  
Author(s):  
Karine Hellemans ◽  
Karen Kerckhofs ◽  
Jean-Claude Hannaert ◽  
Geert Martens ◽  
Paul Van Veldhoven ◽  
...  
Keyword(s):  
Beta Cell ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Cell Protection ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Agonists ◽  
Beta Cell Protection

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

2008 ◽  
Vol 99 (01) ◽  
pp. 86-95 ◽  
Author(s):  
Sherry L Spinelli ◽  
Stephen J Pollock ◽  
Thomas I Murant ◽  
Jamie J O’Brien ◽  
Neil Blumberg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Platelet Activation ◽  
Human Platelets ◽  
Retinoid X Receptor ◽  
Complex Spectrum ◽  
Peroxisome Proliferator ◽  
Monocytic Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
New Findings

SummaryPeroxisome 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.

scholarly journals Attenuation of Colon Inflammation through Activators of the Retinoid X Receptor (Rxr)/Peroxisome Proliferator–Activated Receptor γ (Pparγ) Heterodimer

2001 ◽  
Vol 193 (7) ◽  
pp. 827-838 ◽  
Author(s):  
Pierre Desreumaux ◽  
Laurent Dubuquoy ◽  
Sophie Nutten ◽  
Michel Peuchmaur ◽  
Walter Englaro ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Synergistic Effects ◽  
Survival Rates ◽  
Nuclear Factor Κb ◽  
Retinoid X Receptor ◽  
Trinitrobenzene Sulfonic Acid ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Colon Inflammation

The peroxisome proliferator–activated receptor γ (PPARγ) is highly expressed in the colon mucosa and its activation has been reported to protect against colitis. We studied the involvement of PPARγ and its heterodimeric partner, the retinoid X receptor (RXR) in intestinal inflammatory responses. PPARγ1/− and RXRα1/− mice both displayed a significantly enhanced susceptibility to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis compared with their wild-type littermates. A role for the RXR/PPARγ heterodimer in the protection against colon inflammation was explored by the use of selective RXR and PPARγ agonists. TNBS-induced colitis was significantly reduced by the administration of both PPARγ and RXR agonists. This beneficial effect was reflected by increased survival rates, an improvement of macroscopic and histologic scores, a decrease in tumor necrosis factor α and interleukin 1β mRNA levels, a diminished myeloperoxidase concentration, and reduction of nuclear factor κB DNA binding activity, c-Jun NH2-terminal kinase, and p38 activities in the colon. When coadministered, a significant synergistic effect of PPARγ and RXR ligands was observed. In combination, these data demonstrate that activation of the RXR/PPARγ heterodimer protects against colon inflammation and suggest that combination therapy with both RXR and PPARγ ligands might hold promise in the clinic due to their synergistic effects.

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