Functional interactions of peroxisome proliferator-activated receptor, retinoid-X receptor, and Sp1 in the transcriptional regulation of the acyl-coenzyme-A oxidase promoter

1995 ◽  
Vol 9 (2) ◽  
pp. 219-231 ◽  
Author(s):  
G. Krey
Keyword(s):  
Transcriptional Regulation ◽  
Coenzyme A ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Functional Interactions ◽  
Acyl Coenzyme A

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 Diet Modifies Pioglitazone’s Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Sakil Kulkarni ◽  
Jiansheng Huang ◽  
Eric Tycksen ◽  
Paul F. Cliften ◽  
David A. Rudnick
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Transcriptional Regulation ◽  
Mitochondrial Gene ◽  
Peroxisome Proliferator ◽  
Large Set ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Insulin Resistant

Pioglitazone (Pio) is a thiazolidinedione (TZD) insulin-sensitizing drug whose effects result predominantly from its modulation of the transcriptional activity of peroxisome proliferator-activated-receptor-gamma (PPARγ). Pio is used to treat human insulin-resistant diabetes and also frequently considered for treatment of nonalcoholic steatohepatitis (NASH). In both settings, Pio’s beneficial effects are believed to result primarily from its actions on adipose PPARγ activity, which improves insulin sensitivity and reduces the delivery of fatty acids to the liver. Nevertheless, a recent clinical trial showed variable efficacy of Pio in human NASH. Hepatocytes also express PPARγ, and such expression increases with insulin resistance and in nonalcoholic fatty liver disease (NAFLD). Furthermore, mice that overexpress hepatocellular PPARγ and Pio-treated mice with extrahepatic PPARγ gene disruption develop features of NAFLD. Thus, Pio’s direct impact on hepatocellular gene expression might also be a determinant of this drug’s ultimate influence on insulin resistance and NAFLD. Previous studies have characterized Pio’s PPARγ-dependent effects on hepatic expression of specific adipogenic, lipogenic, and other metabolic genes. However, such transcriptional regulation has not been comprehensively assessed. The studies reported here address that consideration by genome-wide comparisons of Pio’s hepatic transcriptional effects in wildtype (WT) and liver-specific PPARγ-knockout (KO) mice given either control or high-fat (HFD) diets. The results identify a large set of hepatic genes for which Pio’s liver PPARγ-dependent transcriptional effects are concordant with its effects on RXR-DNA binding in WT mice. These data also show that HFD modifies Pio’s influence on a subset of such transcriptional regulation. Finally, our findings reveal a broader influence of Pio on PPARγ-dependent hepatic expression of nuclear genes encoding mitochondrial proteins than previously recognized. Taken together, these studies provide new insights about the tissue-specific mechanisms by which Pio affects hepatic gene expression and the broad scope of this drug’s influence on such regulation.

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.

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