scholarly journals PPARαLigands as Antitumorigenic and Antiangiogenic Agents

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Ambra Pozzi ◽  
Jorge H. Capdevila
Keyword(s):  
Target Genes ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Antiangiogenic Agents ◽  
Peroxisome Proliferator ◽  
Cell Functions ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members—PPARα, PPARδ, and PPARγ—that differ in their cell and tissue distribution as well as in their target genes. PPARαis abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPARα, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we focus on the contribution of PPARαto tumor and endothelial cell functions and provide compelling evidence that PPARαcan be viewed as a new class of ligand activated tumor “suppressor” gene with antiangiogenic and antitumorigenic activities. Given that PPAR ligands are currently used in medicine as hypolipidemic drugs with excellent tolerance and limited toxicity, PPARαactivation might offer a novel and potentially low-toxic approach for the treatment of tumor-associated angiogenesis and cancer.

scholarly journals The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10573
Author(s):  
Jesús Porcuna ◽  
Jorge Mínguez-Martínez ◽  
Mercedes Ricote
Keyword(s):  
Metabolic Disorders ◽  
Target Genes ◽  
Dna Methyltransferases ◽  
Nutrient Sensing ◽  
Peroxisome Proliferator ◽  
Obesity And Diabetes ◽  
Histone Modifiers ◽  
Non Coding Rnas ◽  
Peroxisome Proliferator Activated Receptors ◽  
Epigenetic Modulation

Peroxisome proliferator-activated receptors (PPARs) are ligand-modulated nuclear receptors that play pivotal roles in nutrient sensing, metabolism, and lipid-related processes. Correct control of their target genes requires tight regulation of the expression of different PPAR isoforms in each tissue, and the dysregulation of PPAR-dependent transcriptional programs is linked to disorders, such as metabolic and immune diseases or cancer. Several PPAR regulators and PPAR-regulated factors are epigenetic effectors, including non-coding RNAs, epigenetic enzymes, histone modifiers, and DNA methyltransferases. In this review, we examine advances in PPARα and PPARγ-related epigenetic regulation in metabolic disorders, including obesity and diabetes, immune disorders, such as sclerosis and lupus, and a variety of cancers, providing new insights into the possible therapeutic exploitation of PPAR epigenetic modulation.

scholarly journals Dysregulation of the Peroxisome Proliferator-Activated Receptor Target Genes by XPD Mutations

2005 ◽  
Vol 25 (14) ◽  
pp. 6065-6076 ◽  
Author(s):  
Emmanuel Compe ◽  
Pascal Drané ◽  
Camille Laurent ◽  
Karin Diderich ◽  
Cathy Braun ◽  
...  
Keyword(s):  
Target Genes ◽  
Genetic Disorders ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Independent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pol Ii ◽  
Knowing That ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands

ABSTRACT Mutations in the XPD subunit of TFIIH give rise to human genetic disorders initially defined as DNA repair syndromes. Nevertheless, xeroderma pigmentosum (XP) group D (XP-D) patients develop clinical features such as hypoplasia of the adipose tissue, implying a putative transcriptional defect. Knowing that peroxisome proliferator-activated receptors (PPARs) are implicated in lipid metabolism, we investigated the expression of PPAR target genes in the adipose tissues and the livers of XPD-deficient mice and found that (i) some genes are abnormally overexpressed in a ligand-independent manner which parallels an increase in the recruitment of RNA polymerase (pol) II but not PPARs on their promoter and (ii) upon treatment with PPAR ligands, other genes are much less induced compared to the wild type, which is due to a lower recruitment of both PPARs and RNA pol II. The defect in transactivation by PPARs is likely attributable to their weaker phosphorylation by the cdk7 kinase of TFIIH. Having identified the phosphorylated residues in PPAR isotypes, we demonstrate how their transactivation defect in XPD-deficient cells can be circumvented by overexpression of either a wild-type XPD or a constitutively phosphorylated PPAR S/E. This work emphasizes that underphosphorylation of PPARs affects their transactivation and consequently the expression of PPAR target genes, thus contributing in part to the XP-D phenotype.

scholarly journals Peroxisome Proliferator-Activated Receptors and Acute Lung Injury

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-8 ◽  
Author(s):  
Rosanna Di Paola ◽  
Salvatore Cuzzocrea
Keyword(s):  
Immune Responses ◽  
Metabolic Pathways ◽  
Target Genes ◽  
Inflammatory Diseases ◽  
Nuclear Hormone Receptor ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARs regulate several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Recently, PPARs and their respective ligands have been implicated as regulators of cellular inflammatory and immune responses. These molecules are thought to exert anti-inflammatory effects by negatively regulating the expression of proinflammatory genes. Several studies have demonstrated that PPAR ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the lung. This review will outline the anti-inflammatory effects of PPARs and PPAR ligands and discuss their potential therapeutic effects in animal models of inflammatory lung disease.

scholarly journals Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions

2021 ◽  
Vol 22 (1) ◽  
pp. 433
Author(s):  
Lin Peng ◽  
Huixia Yang ◽  
Yao Ye ◽  
Zhi Ma ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Recurrent Miscarriage ◽  
Migration And Invasion ◽  
Peroxisome Proliferator ◽  
Treatment And Prevention ◽  
Peroxisome Proliferator Activated Receptors ◽  
Adverse Pregnancy ◽  
Underlying Mechanisms ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) belong to the transcription factor family, and they are highly expressed in all types of trophoblast during pregnancy. The present review discusses currently published papers that are related to the regulation of PPARs via lipid metabolism, glucose metabolism, and amino acid metabolism to affect trophoblast physiological conditions, including differentiation, maturation, secretion, fusion, proliferation, migration, and invasion. Recent pieces of evidence have proven that the dysfunctions of PPARs in trophoblast lead to several related pregnancy diseases such as recurrent miscarriage, preeclampsia, intrauterine growth restriction, and gestational diabetes mellitus. Moreover, the underlying mechanisms of PPARs in the control of these processes have been discussed as well. Finally, this review’s purposes are to provide more knowledge about the role of PPARs in normal and disturbed pregnancy with trophoblast, so as to find PPAR ligands as a potential therapeutic target in the treatment and prevention of adverse pregnancy outcomes.

scholarly journals PPARgene: A Database of Experimentally Verified and Computationally Predicted PPAR Target Genes

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Li Fang ◽  
Man Zhang ◽  
Yanhui Li ◽  
Yan Liu ◽  
Qinghua Cui ◽  
...  
Keyword(s):  
In Silico ◽  
Target Gene ◽  
Target Genes ◽  
Prediction Method ◽  
Peroxisome Proliferator ◽  
Physiological Processes ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Throughput Gene Expression ◽  
Responsive Element ◽  
Target Gene Transcription

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear receptor superfamily. Upon ligand binding, PPARs activate target gene transcription and regulate a variety of important physiological processes such as lipid metabolism, inflammation, and wound healing. Here, we describe the first database of PPAR target genes, PPARgene. Among the 225 experimentally verified PPAR target genes, 83 are for PPARα, 83 are for PPARβ/δ, and 104 are for PPARγ. Detailed information including tissue types, species, and reference PubMed IDs was also provided. In addition, we developed a machine learning method to predict novel PPAR target genes by integratingin silicoPPAR-responsive element (PPRE) analysis with high throughput gene expression data. Fivefold cross validation showed that the performance of this prediction method was significantly improved compared to thein silicoPPRE analysis method. The prediction tool is also implemented in the PPARgene database.

scholarly journals Peroxisome Proliferator-Activated Receptor Subtype- and Cell-Type-Specific Activation of Genomic Target Genes upon Adenoviral Transgene Delivery

2006 ◽  
Vol 26 (15) ◽  
pp. 5698-5714 ◽  
Author(s):  
Ronni Nielsen ◽  
Lars Grøntved ◽  
Hendrik G. Stunnenberg ◽  
Susanne Mandrup
Keyword(s):  
Target Genes ◽  
Receptor Subtype ◽  
Peroxisome Proliferator ◽  
Cell Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Events ◽  
Adenoviral Delivery ◽  
Cell Type Specific ◽  
Peroxisome Proliferator Activated Receptors ◽  
The Individual

ABSTRACT Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes. We demonstrate that PPARγ2 possesses considerable ligand-dependent as well as independent transactivation potential and that agonists increase the occupancy of PPARγ2/retinoid X receptor at PPAR response elements. Intriguingly, by direct comparison of the PPARs (α, γ, and β/δ), we show that the subtypes have very different abilities to gain access to target sites and that in general the genomic occupancy correlates with the ability to activate the corresponding target gene. In addition, the specificity and potency of activation by PPAR subtypes are highly dependent on the cell type. Thus, PPAR subtype-specific activation of genomic target genes involves an intricate interplay between the properties of the subtype- and cell-type-specific settings at the individual target loci.

scholarly journals Peroxisome-proliferator-activated receptors and the control of levels of prostaglandin-endoperoxide synthase 2 by arachidonic acid in the bovine uterus

2007 ◽  
Vol 406 (1) ◽  
pp. 175-183 ◽  
Author(s):  
E. Linda R. Sheldrick ◽  
Kamila Derecka ◽  
Elaine Marshall ◽  
Evonne C. Chin ◽  
Louise Hodges ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Stromal Cells ◽  
Time Course ◽  
Nuclear Factor Κb ◽  
Peroxisome Proliferator ◽  
Endometrial Stromal Cells ◽  
Prostaglandin Endoperoxide ◽  
Prostaglandin Endoperoxide Synthase ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands

Arachidonic acid is a potential paracrine agent released by the uterine endometrial epithelium to induce PTGS2 [PG (prostaglandin)-endoperoxide synthase 2] in the stroma. In the present study, bovine endometrial stromal cells were used to determine whether PTGS2 is induced by arachidonic acid in stromal cells, and to investigate the potential role of PPARs (peroxisome-proliferator-activated receptors) in this effect. Arachidonic acid increased PTGS2 levels up to 7.5-fold within 6 h. The cells expressed PPARα and PPARδ (also known as PPARβ) (but not PPARγ). PTGS2 protein level was increased by PPAR agonists, including polyunsaturated fatty acids, synthetic PPAR ligands, PGA1 and NSAIDs (non-steroidal anti-inflammatory drugs) with a time course resembling that of arachidonic acid. Use of agonists and antagonists indicated PPARα (but not PPARδ or PPARγ) was responsible for PTGS2 induction. PTGS2 induction by arachidonic acid did not require PG synthesis. PTGS2 levels were increased by the PKC (protein kinase C) activators 4β-PMA and PGF2α, and the effects of arachidonic acid, NSAIDs, synthetic PPAR ligands and 4β-PMA were blocked by PKC inhibitors. This is consistent with PPAR phosphorylation by PKC. Induction of PTGS2 protein by 4β-PMA in the absence of a PPAR ligand was decreased by the NF-κB (nuclear factor κB) inhibitors MG132 and parthenolide, suggesting that PKC acted through NF-κB in addition to PPAR phosphorylation. Use of NF-κB inhibitors allowed the action of arachidonic acid as a PPAR agonist to be dissociated from an effect through PKC. The results are consistent with the hypothesis that arachidonic acid acts via PPARα to increase PTGS2 levels in bovine endometrial stromal cells.

scholarly journals Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoyan Sheng ◽  
Yuebo Zhang ◽  
Zhenwei Gong ◽  
Cheng Huang ◽  
Ying Qin Zang
Keyword(s):  
Insulin Resistance ◽  
Target Genes ◽  
Water Extract ◽  
Food Preparation ◽  
Peroxisome Proliferator ◽  
Cinnamon Extract ◽  
Diet Induced Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Caloric Diet

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARγandα, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) anddb/dbmice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptorsγandα(PPARγ/α) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARγand PPARαare activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARγandα, and may be an alternative to PPARγactivator in managing obesity-related diabetes and hyperlipidemia.

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