scholarly journals Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Oxana Yu. Kytikova ◽  
Juliy M. Perelman ◽  
Tatyana P. Novgorodtseva ◽  
Yulia K. Denisenko ◽  
Viktor P. Kolosov ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Treatment Effectiveness ◽  
Therapeutic Agents ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Signaling Mechanisms ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function ◽  
Ppar Ligands ◽  
Potential Use

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

scholarly journals Peroxisome Proliferator-Activated Receptor Delta: A Conserved Director of Lipid Homeostasis through Regulation of the Oxidative Capacity of Muscle

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Pieter de Lange ◽  
Assunta Lombardi ◽  
Elena Silvestri ◽  
Fernando Goglia ◽  
Antonia Lanni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Transcriptional Program ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisome Proliferator Activated Receptors ◽  
Metabolic Action

The peroxisome proliferator-activated receptors (PPARs), which are ligand-inducible transcription factors expressed in a variety of tissues, have been shown to perform key roles in lipid homeostasis. In physiological situations such as fasting and physical exercise, one PPAR subtype, PPARδ, triggers a transcriptional program in skeletal muscle leading to a switch in fuel usage from glucose/fatty acids to solely fatty acids, thereby drastically increasing its oxidative capacity. The metabolic action of PPARδ has also been verified in humans. In addition, it has become clear that the action of PPARδ is not restricted to skeletal muscle. Indeed, PPARδ has been shown to play a crucial role in whole-body lipid homeostasis as well as in insulin sensitivity, and it is active not only in skeletal muscle (as an activator of fat burning) but also in the liver (where it can activate glycolysis/lipogenesis, with the produced fat being oxidized in muscle) and in the adipose tissue (by incrementing lipolysis). The main aim of this review is to highlight the central role for activated PPARδ in the reversal of any tendency toward the development of insulin resistance.

scholarly journals Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

scholarly journals The Role of Peroxisome Proliferator-Activated Receptors in Pulmonary Vascular Disease

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Rachel E. Nisbet ◽  
Roy L. Sutliff ◽  
C. Michael Hart
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Nuclear Hormone Receptor ◽  
Pulmonary Vascular Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Function

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily that regulate diverse physiological processes ranging from lipogenesis to inflammation. Recent evidence has established potential roles of PPARs in both systemic and pulmonary vascular disease and function. Existing treatment strategies for pulmonary hypertension, the most common manifestation of pulmonary vascular disease, are limited by an incomplete understanding of the underlying disease pathogenesis and lack of efficacy indicating an urgent need for new approaches to treat this disorder. Derangements in pulmonary endothelial-derived mediators and endothelial dysfunction have been shown to play a pivotal role in pulmonary hypertension pathogenesis. Therefore, the following review will focus on selected mediators implicated in pulmonary vascular dysfunction and evidence that PPARs, in particular PPARγ, participate in their regulation and may provide a potential novel therapeutic target for the treatment of pulmonary hypertension.

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 Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

2014 ◽  
Vol 220 (3) ◽  
pp. 345-359 ◽  
Author(s):  
M Kurtz ◽  
E Capobianco ◽  
V Careaga ◽  
N Martinez ◽  
M B Mazzucco ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Olive Oil ◽  
Lung Development ◽  
Maternal Diabetes ◽  
Diabetic Rats ◽  
Lipid Homeostasis ◽  
Safflower Oil ◽  
Peroxisome Proliferator ◽  
Fetal Lungs ◽  
Ppar Ligands

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect ofin vivoactivation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4(LTB4, PPARα ligand) or 15deoxyΔ12,14prostaglandin J2(15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4and partially restored by 15dPGJ2in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

The Journey of Thiazolidinediones as Modulators of PPARs for the Management of Diabetes: A Current Perspective

2019 ◽  
Vol 25 (23) ◽  
pp. 2540-2554 ◽  
Author(s):  
Waquar Ahsan
Keyword(s):  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Current Perspective ◽  
Drug Designing ◽  
Peroxisome Proliferator Activated Receptors ◽  
To Come ◽  
Ppar Ligands ◽  
A Current

Peroxisome Proliferator-Activated Receptors (PPARs) also known as glitazone receptors are a family of receptors that regulate the expression of genes and have an essential role in carbohydrate, lipid and protein metabolism apart from other functions. PPARs come in 3 sub-types: PPAR-α, PPAR-β/δ and PPAR-γ - with PPAR-γ having 2 isoforms - γ1 and γ2. Upon activation, the PPARs regulate the transcription of various genes involved in lipid and glucose metabolism, adipocyte differentiation, increasing insulin sensitivity, prevention of oxidative stress and to a certain extent, modulation of immune responses via macrophages that have been implicated in the pathogenesis of insulin resistance. Hence, PPARs are an attractive molecular target for designing new anti-diabetic drugs. This has led to a boost in the research efforts directed towards designing of PPAR ligands - particularly ones that can selectively and specifically activate one or more of the PPAR subtypes. Though, PPAR- γ full agonists such as Thiazolidinediones (TZDs) are well established agents for dyslipidemia and type 2 diabetes mellitus (T2D), the side effect profile associated with TZDs has potentiated an imminent need to come up with newer agents that act through this pathway. Several newer derivatives having TZD scaffold have been designed using structure based drug designing technique and computational tools and tested for their PPAR binding affinity and efficacy in combating T2D and some have shown promising activities. This review would focus on the role of PPARs in the management of T2D; recently reported TZD derivatives which acted as agonists of PPAR- γ and its subtypes and are potentially useful in the new drug discovery for the disease.

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.

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