scholarly journals Time course- and dose-dependent analysis of the rosiglitazone (Rosi)-dependent and peroxisome proliferator-activated receptor-γ (PPARγ/Pparg)-dependent transcriptomes in mouse thoracic aorta

2015 ◽  
Author(s):  
HL Keen
Keyword(s):  
Thoracic Aorta ◽  
Time Course ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dose Dependent

scholarly journals Human Endometrial Stromal Cell Differentiation is Stimulated by PPARβ/δ Activation: New Targets for Infertility?

2020 ◽  
Vol 105 (9) ◽  
pp. 2983-2995 ◽  
Author(s):  
Jie Yu ◽  
Sarah L Berga ◽  
Wei Zou ◽  
Augustine Rajakumar ◽  
Mingfei Man ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Growth Factor ◽  
Connexin 43 ◽  
Time Course ◽  
Estrogen Receptor Α ◽  
Peroxisome Proliferator ◽  
Endometrial Stromal Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Therapeutic Benefits

Abstract Context Implantation is a reproductive bottleneck in women, regulated by fluctuations in ovarian steroid hormone concentrations. However, other nuclear receptor ligands are modifiers of endometrial differentiation leading to successful pregnancy. In the present study we analyzed the effects of peroxisome-proliferator-activated receptor β/δ (PPARβ/δ) activation on established cellular biomarkers of human endometrial differentiation (decidualization). Objective The objective of this work is to test the effects of PPARβ/δ ligation on human endometrial cell differentiation. Design Isolated primary human endometrial stromal cells (ESCs) were treated with synthetic (GW0742) or natural (all trans-retinoic acid, RA) ligands of PPARβ/δ, and also with receptor antagonists (GSK0660, PT-S58, and ST247) in the absence or presence of decidualizing hormones (10 nM estradiol, 100 nM progesterone, and 0.5 mM dibutyryl cAMP [3′,5′-cyclic adenosine 5′-monophosphate]). In some cases interleukin (IL)-1β was used as an inflammatory stimulus. Time course and dose-response relationships were evaluated to determine effects on panels of well characterized in vitro biomarkers of decidualization. Results PPARβ/δ, along with estrogen receptor α (ERα) and PR-A and PR-B, were expressed in human endometrial tissue and isolated ESCs. GW0742 treatment enhanced hormone-mediated ESC decidualization in vitro as manifested by upregulation of prolactin, insulin-like growth factor-binding protein 1, IL-11, and vascular endothelial growth factor (VEGF) secretion and also increased expression of ERα, PR-A and PR-B, and connexin 43 (Cx43). RA treatment also increased VEGF, ERα, PR-A, and PR-B and an active, nonphosphorylated isoform of Cx43. IL-1β and PPARβ/δ antagonists inhibited biomarkers of endometrial differentiation. Conclusion Ligands that activate PPARβ/δ augment the in vitro expression of biomarkers of ESC decidualization. By contrast, PPARβ/δ antagonists impaired decidualization markers. Drugs activating these receptors may have therapeutic benefits for embryonic implantation.

scholarly journals Dysregulation of secretion of CXC α-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-γ agonists

2009 ◽  
Vol 16 (4) ◽  
pp. 1299-1311 ◽  
Author(s):  
Alessandro Antonelli ◽  
Silvia Martina Ferrari ◽  
Poupak Fallahi ◽  
Silvia Frascerra ◽  
Simona Piaggi ◽  
...  
Keyword(s):  
Primary Cultures ◽  
Cell Types ◽  
Interferon Γ ◽  
Antiproliferative Effect ◽  
Peroxisome Proliferator ◽  
Papillary Thyroid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Similar Dose ◽  
Factor Α ◽  
Dose Dependent

In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional program including the upregulation of CXCL10 chemokine, which stimulates proliferation and invasion. Furthermore, peroxisome proliferator-activated receptor-γ (PPARγ) activators thiazolidinediones (TZDs) modulate CXCL10 secretion in normal thyroid follicular cells (TFC), and inhibit PTC growth. Until now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs, nor the effect of PPARγ activation. The combined effects of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPARγ activation by TZDs, on CXCL10 secretion and proliferation in these cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was absent under basal conditions; a similar dose-dependent secretion of CXCL10 was induced by IFNγ in both cell types. TNFα alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFNγ+TNFα induced a synergistic CXCL10 release in both cell types; however, a secretion more than ten times higher was induced in PTCs. Treatment of TFC with TZDs dose-dependently suppressed IFNγ+TNFα-induced CXCL10 release, while TZDs stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by TZDs was observed only in PTCs. In conclusion, a dysregulation of CXCL10 secretion has been shown in PTCs. In fact, a CXCL10 secretion more than ten times higher has been induced by IFNγ+TNFα in PTCs with respect to TFC. Moreover, TZDs inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The effect of TZDs on CXCL10 was unrelated to the significant antiproliferative effect in PTCs.

scholarly journals Peroxisome Proliferator-Activated Receptor γ Target Gene Encoding a Novel Angiopoietin-Related Protein Associated with Adipose Differentiation

2000 ◽  
Vol 20 (14) ◽  
pp. 5343-5349 ◽  
Author(s):  
J. Cliff Yoon ◽  
Troy W. Chickering ◽  
Evan D. Rosen ◽  
Barry Dussault ◽  
Yubin Qin ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Time Course ◽  
Target Gene ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Isolation And Characterization ◽  
Adipose Differentiation ◽  
Novel Target

ABSTRACT The nuclear receptor peroxisome proliferator-activated receptor γ regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation and characterization of a novel target gene induced by PPARγ ligands, termed PGAR (for PPARγ angiopoietin related), which encodes a novel member of the angiopoietin family of secreted proteins. The transcriptional induction of PGAR follows a rapid time course typical of immediate-early genes and occurs in the absence of protein synthesis. The expression of PGAR is predominantly localized to adipose tissues and placenta and is consistently elevated in genetic models of obesity. Hormone-dependent adipocyte differentiation coincides with a dramatic early induction of the PGAR transcript. Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of systemic lipid metabolism or glucose homeostasis.

scholarly journals Leptin Rapidly Induces the Expression of Metabolic and Myokine Genes in C2C12 Muscle Cells to Regulate Nutrient Partition and Oxidation

2015 ◽  
Vol 35 (1) ◽  
pp. 92-103 ◽  
Author(s):  
Yuriy Nozhenko ◽  
Ana M. Rodríguez ◽  
Andreu Palou
Keyword(s):  
Time Course ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Muscle Cells ◽  
Pyruvate Dehydrogenase Kinase ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

Background: Skeletal muscle can experience pronounced metabolic adaptations in response to extrinsic stimuli, and expresses leptin receptor (OB-Rb). We aimed to further the understanding of leptin effects on muscle cells, by studying the expression of key energy metabolism genes in C2C12 myotubes. Methods: We performed a dose-time-dependent study with physiological concentrations of leptin: 5, 10 and 50ng/ml, for 0, 30', 3h, 6h, 12h and 24h, also monitoring time-course changes in non-treated cells. mRNA levels were analyzed by RT-qPCR and peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) protein levels by western blot. Results: The most significant effects were observed with 50ng/ml leptin. In the short-term (30' and/or 3h), leptin significantly induced the expression of PGC1α, muscle carnitine palmitoyl transferase 1 (mCPT1), uncoupling protein 3 (UCP3), OB-Rb, Insulin receptor (InsR) and interleukins 6 and 15 (IL6, IL15). There was a decrease in mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and mCPT1 in the long-term (24h). PGC1α protein levels were increased (24h). Conclusion: Leptin rapidly induces the expression of genes important for its own response and the control of metabolic fuels, with the rapid responses of the genes encoding the master regulator PGC1α, mCPT1, UCP3, PDK4 and the signaling secretory molecule IL6 particularly interesting.

scholarly journals Cevoglitazar, a Novel Peroxisome Proliferator-Activated Receptor-α/γ Dual Agonist, Potently Reduces Food Intake and Body Weight in Obese Mice and Cynomolgus Monkeys

2010 ◽  
Vol 31 (3) ◽  
pp. 404-405
Author(s):  
Hong Chen ◽  
Beatriz Dardik ◽  
Ling Qiu ◽  
Xianglin Ren ◽  
Shari L. Caplan ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Plasma Levels ◽  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cynomolgus Monkeys ◽  
Dose Dependent ◽  
Dual Agonist

ABSTRACT Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-α and -γ subtypes. Dual activation of PPARα and -γ is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 μg/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.

Peroxisome proliferators compete and ameliorate Hcy-mediated endocardial endothelial cell activation

2002 ◽  
Vol 283 (4) ◽  
pp. C1073-C1079 ◽  
Author(s):  
Matthew J. Hunt ◽  
Suresh C. Tyagi
Keyword(s):  
Fluorescence Quenching ◽  
Conformational Changes ◽  
Cell Activation ◽  
Intercellular Adhesion Molecule ◽  
Affinity Column ◽  
Peroxisome Proliferator ◽  
Endothelial Cell Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Dose Dependent

To determine whether homocysteine (Hcy)-mediated activation of endocardial endothelial (EE) cells is ameliorated by peroxisome proliferator-activated receptor (PPAR), we isolated EE cells from mouse endocardium. Matrix metalloproteinase (MMP) activity and intercellular adhesion molecule (ICAM)-1 in EE cells were measured in the presence and absence of Hcy, and ciprofibrate (CF; PPAR-α agonist) or 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2; PPAR-γ agonist) by zymography and Western blot analyses, respectively. Results suggest that Hcy-mediated MMP activation and ICAM-1 expression are ameliorated by CF and PGJ2. To test the hypothesis that Hcy competes with other ligands for binding to PPARα and -γ, we prepared cardiac nuclear extracts. Extracts were loaded onto an Hcy-cellulose affinity column. Bound proteins were eluted with CF and PGJ2. To determine conformational changes in PPAR upon binding to Hcy, we measured PPAR fluorescence at 334 nm. Dose-dependent increase in PPAR fluorescence demonstrated a primary binding affinity of 0.32 ± 0.06 μM. There was dose-dependent quenching of PPAR fluorescence by fluorescamine-homocysteine (F-Hcy). PPAR-α fluorescence quenching was abrogated by the addition of CF but not by PGJ2. PPAR-γ fluorescence quenching was abrogated by the addition of PGJ2 but not by CF. These results suggest that Hcy competes with CF and PGJ2 for binding to PPAR-α and -γ, respectively, indicating a role of PPAR in amelioration of Hcy-mediated EE dysfunction.

scholarly journals Protective Effects of Peroxisome Proliferator-Activated Receptor-αAgonist, Wy14643, on Hypoxia/Reoxygenation Injury in Primary Rat Hepatocytes

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ke Chen ◽  
Yuan-Hai Li ◽  
Si-Qi Xu ◽  
Sheng-Hong Hu ◽  
Lei Zhang
Keyword(s):  
Rat Hepatocytes ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protective Effects ◽  
Primary Hepatocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Group A ◽  
Reoxygenation Injury ◽  
Dose Dependent ◽  
Significant Protective Effect

This study investigates the effects and possible mechanism of an agonist of PPARα, Wy14643, on primary hepatocytes subjected to H/R injury in rats. H/R induced a significant increase ALT, AST, MDA in the culture medium and ROS in the hepatocytes. These effects were reversed by pretreatment with Wy14643 in the dose-dependent manner. The activity of SOD and the level of GSH in the hepatocytes were decreased after H/R, which were increased by Wy14643 pretreatment. Moreover, the mRNA expressions of PPARαsignificantly increased in H/R+Wy14643 groups when compared with that in H/R group. A PPARαagonist, Wy14643, exerts significant protective effect against H/R injury in primary hepatocytes via PPARαactivation and attenuating oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document