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 Peroxisome Proliferator-Activated Receptors and Shock State

2006 ◽  
Vol 6 ◽  
pp. 1770-1782 ◽  
Author(s):  
Emanuela Esposito ◽  
Salvatore Cuzzocrea ◽  
Rosaria Meli
Keyword(s):  
Transcription Factors ◽  
Energy Homeostasis ◽  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Shock State ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors ◽  
Inflammatory Molecules

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of PPARs have been identified: alpha, beta/delta, and gamma, encoded by different genes and distributed in various tissues. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and, thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert anti-inflammatory effects by inhibiting the induction of proinflammatory cytokines, adhesion molecules, and extracellular matrix proteins, or by stimulating the production of anti-inflammatory molecules. Moreover, PPARs modulate the proliferation, differentiation, and survival of immune cells. This review presents the current state of knowledge regarding the involvement of PPARs in the control of inflammatory response, and their potential therapeutic applications in several types of shock, as well as hemorrhagic, septic, and nonseptic shock.

PPAR Ligands Containing Stilbene Scaffold

2019 ◽  
Vol 19 (19) ◽  
pp. 1599-1610 ◽  
Author(s):  
Marialuigia Fantacuzzi ◽  
Barbara De Filippis ◽  
Rosa Amoroso ◽  
Letizia Giampietro
Keyword(s):  
The Body ◽  
Peroxisome Proliferator ◽  
Signaling Proteins ◽  
Health Promoting ◽  
Pparγ Agonists ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pharmacological Potential ◽  
Ppar Ligands ◽  
New Generation

: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors which belong to the ligand-activated nuclear receptor superfamily. They are ubiquitously expressed throughout the body. So far, three major subtypes have been identified, PPARα, PPARβ/δ and PPARγ. They are crucial for lipid and glucose metabolism and are also involved in the regulation of several types of tumors, inflammation, cardiovascular diseases and infertility. The importance of these transcription factors in physiology and pathophysiology has been largely investigated. : Synthetic PPAR ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists) while a new generation of dual agonists reveals hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action. Many natural ligands, including polyphenolic compounds, influence the expression of these receptors. They have several health-promoting properties, including antioxidant, anti-inflammatory, and antineoplastic activities. Resveratrol, a stilbene polyphenol, is a biological active modulator of several signaling proteins, including PPARs. Given the enormous pharmacological potential of resveratrol, stilbene-based medicinal chemistry had a rapid increase covering various areas of research. : The present review discusses ligands of PPARs that contain stilbene scaffold and summarises the different types of compounds on the basis of chemical structure.

How nuclear receptors tell time

2009 ◽  
Vol 107 (6) ◽  
pp. 1965-1971 ◽  
Author(s):  
Michèle Teboul ◽  
Aline Gréchez-Cassiau ◽  
Fabienne Guillaumond ◽  
Franck Delaunay
Keyword(s):  
Nuclear Receptors ◽  
Target Genes ◽  
Clock Genes ◽  
Estrogen Receptor Α ◽  
Nuclear Hormone Receptor ◽  
Circadian Clocks ◽  
Orphan Receptor ◽  
Peroxisome Proliferator ◽  
Peripheral Clocks ◽  
Peroxisome Proliferator Activated Receptors

Most organisms adapt their behavior and physiology to the daily changes in their environment through internal (∼24 h) circadian clocks. In mammals, this time-keeping system is organized hierarchically, with a master clock located in the suprachiasmatic nuclei of the hypothalamus that is reset by light, and that, in turn, coordinates the oscillation of local clocks found in all cells. Central and peripheral clocks control, in a highly tissue-specific manner, hundreds of target genes, resulting in the circadian regulation of most physiological processes. A great deal of knowledge has accumulated during the last decade regarding the molecular basis of mammalian circadian clocks. These studies have collectively demonstrated how a set of clock genes and their protein products interact together in complex feedback transcriptional/translational loops to generate 24-h oscillations at the molecular, cellular, and organism levels. In recent years, a number of nuclear receptors (NRs) have been implicated as important regulators of the mammalian clock mechanism. REV-ERB and retinoid-related orphan receptor NRs regulate directly the core feedback loop and increase its robustness. The glucocorticoid receptor mediates the synchronizing effect of glucocorticoid hormones on peripheral clocks. Other NR family members, including the orphan NR EAR2, peroxisome proliferator activated receptors-α/γ, estrogen receptor-α, and retinoic acid receptors, are also linked to the clockwork mechanism. These findings together establish nuclear hormone receptor signaling as an integral part of the circadian timing system.

scholarly journals Elucidation of the Anti-Inflammatory Mechanisms of Bupleuri and Scutellariae Radix Using System Pharmacological Analyses

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Shen ◽  
Zhenyu Zhao ◽  
Hao Wang ◽  
Zihu Guo ◽  
Benxiang Hu ◽  
...  
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Active Components ◽  
Scutellariae Radix ◽  
Combined Application ◽  
Anti Inflammatory ◽  
Bupleuri Radix

Objective. This study was aimed at elucidating the molecular mechanisms underlying the anti-inflammatory effect of the combined application of Bupleuri Radix and Scutellariae Radix and explored the potential therapeutic efficacy of these two drugs on inflammation-related diseases. Methods. After searching the databases, we collected the active ingredients of Bupleuri Radix and Scutellariae Radix and calculated their oral bioavailability (OB) and drug-likeness (DL) based on the absorption-distribution-metabolism-elimination (ADME) model. In addition, we predicted the drug targets of the selected active components based on weighted ensemble similarity (WES) and used them to construct a drug-target network. Gene ontology (GO) analysis and KEGG mapper tools were performed on these predicted target genes. Results. We obtained 30 compounds from Bupleuri Radix and Scutellariae Radix of good quality as indicated by ADME assays, which possess potential pharmacological activity. These 30 ingredients have a total of 121 potential target genes, which are involved in 24 biological processes related to inflammation. Conclusions. Combined application of Bupleuri Radix and Scutellariae Radix was found not only to directly inhibit the synthesis and release of inflammatory cytokines, but also to have potential therapeutic effects against inflammation-induced pain. In addition, a combination therapy of these two drugs exhibited systemic treatment efficacy and provided a theoretical basis for the development of drugs against inflammatory diseases.

scholarly journals Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

2004 ◽  
Vol 2004 (3) ◽  
pp. 156-166 ◽  
Author(s):  
Jihan Youssef ◽  
Mostafa Badr
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Late Phase ◽  
Common Mechanism ◽  
Peroxisome Proliferator ◽  
Initiation Phase ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα,δ,γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases.

scholarly journals PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming

2021 ◽  
Vol 22 (14) ◽  
pp. 7354
Author(s):  
Stefan Blunder ◽  
Petra Pavel ◽  
Deborah Minzaghi ◽  
Sandrine Dubrac
Keyword(s):  
Atopic Dermatitis ◽  
Hormone Receptors ◽  
Target Genes ◽  
Skin Diseases ◽  
Retinoic Acid Receptor ◽  
Skin Inflammation ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Keratinocyte Proliferation ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), β or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARβ/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARβ/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARβ/δ to alleviate skin inflammation is discussed.

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 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 Therapeutic Effects of PPARαon Neuronal Death and Microvascular Impairment

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Elizabeth P. Moran ◽  
Jian-xing Ma
Keyword(s):  
Vascular Function ◽  
Target Genes ◽  
Microvascular Complications ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Nuclear Hormone Receptor ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Microvascular Impairment

Peroxisome-proliferator activated receptor-alpha (PPARα) is a broadly expressed nuclear hormone receptor and is a transcription factor for diverse target genes possessing a PPAR response element (PPRE) in the promoter region. The PPRE is highly conserved, and PPARs thus regulate transcription of an extensive array of target genes involved in energy metabolism, vascular function, oxidative stress, inflammation, and many other biological processes. PPARαhas potent protective effects against neuronal cell death and microvascular impairment, which have been attributed in part to its antioxidant and anti-inflammatory properties. Here we discuss PPARα’s effects in neurodegenerative and microvascular diseases and also recent clinical findings that identified therapeutic effects of a PPARαagonist in diabetic microvascular complications.

scholarly journals New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ(PPARγ) Antitumour Activity: Perspectives from the Insulin Receptor

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Daniela P. Foti ◽  
Francesco Paonessa ◽  
Eusebio Chiefari ◽  
Antonio Brunetti
Keyword(s):  
Insulin Receptor ◽  
Target Genes ◽  
Tumour Progression ◽  
Antitumour Activity ◽  
Peptide Hormone ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Preclinical Research ◽  
Peroxisome Proliferator Activated Receptor ◽  
Wide Range

The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγis a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγagonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγand activators affect tumours by different mechanisms, involving cell proliferation and differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We recently provided evidence that PPARγand agonists inhibit IR by non canonical, DNA-independent mechanisms affecting IR gene transcription. We conclude that IR may be considered a new PPARγ“target” gene, supporting a potential use of PPARγagonists as antiproliferative agents in selected neoplastic tissues that overexpress the IR.

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