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.

Regulation of dectin-1–mediated dendritic cell activation by peroxisome proliferator–activated receptor-gamma ligand troglitazone

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3569-3574 ◽  
Author(s):  
Grethe Kock ◽  
Anita Bringmann ◽  
Stefanie Andrea Erika Held ◽  
Solveig Daecke ◽  
Annkristin Heine ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Nuclear Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Mitogen Activated Protein

Abstract Dectin-1 is the major receptor for fungal β-glucans. The activation of Dectin-1 leads to the up-regulation of surface molecules on dendritic cells (DCs) and cytokine secretion. Furthermore, Dectin-1 is important for the recruitment of leukocytes and the production of inflammatory mediators. Peroxisome proliferator–activated receptor-γ (PPAR-γ) and its ligands, cyclopentenone prostaglandins or thiazolidinediones, have modulatory effects on B-cell, T-cell, and DC function. In the present study, we analyzed the effects of troglitazone (TGZ), a high-affinity synthetic PPAR-γ ligand, on the Dectin-1–mediated activation of monocyte-derived human DCs. Dectin-1–mediated activation of DCs was inhibited by TGZ, as shown by down-regulation of costimulatory molecules and reduced secretion of cytokines and chemokines involved in T-lymphocyte activation. Furthermore, TGZ inhibited the T-cell–stimulatory capacity of DCs. These effects were not due to a diminished expression of Dectin-1 or to a reduced phosphorylation of spleen tyrosine kinase; they were mediated by the inhibition of downstream signaling molecules such as mitogen-activated protein kinases and nuclear factor-κB. Furthermore, curdlan-mediated accumulation of caspase recruitment domain 9 (CARD9) in the cytosol was inhibited by TGZ. Our data demonstrate that the PPAR-γ ligand TGZ inhibits Dectin-1–mediated activation by interfering with CARD9, mitogen-activated protein kinase, and nuclear factor-κB signaling pathways. This confirms their important role as negative-feedback regulators of potentially harmful inflammatory responses.

Primary chemoprevention of endometrial hyperplasia with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone in the PTEN heterozygote murine model

2008 ◽  
Vol 18 (2) ◽  
pp. 329-338 ◽  
Author(s):  
W. Wu ◽  
J. Celestino ◽  
M. R. Milam ◽  
K. M. Schmeler ◽  
R. R. Broaddus ◽  
...  
Keyword(s):  
Cell Lines ◽  
Murine Model ◽  
Endometrial Hyperplasia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Dose Dependent

PTEN mutations have been implicated in the development of endometrial hyperplasia and subsequent cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists have demonstrated antineoplastic and chemopreventive effects. The purpose of this study was to evaluate the effects of the PPAR-γ agonist rosiglitazone on both PTEN wild type and PTEN null cell lines and in the PTEN heterozygote(+/−) murine model. Hec-1-A (PTEN wild type) and Ishikawa (PTEN null) cells were treated with rosiglitazone. Thirty-five female PTEN+/− mice were genotyped and placed into one of four groups for treatment for 18 weeks: A) PTEN wild type with 4 mg/kg rosiglitazone, B) PTEN+/− mice with vehicle, C) PTEN+/− mice with 4 mg/kg rosiglitazone, and D) PTEN+/− mice with 8 mg/kg rosiglitazone. Proliferation and apoptosis were measured by bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragmentation sites assay. Rosiglitazone caused cell growth inhibition in both Hec-1-A and Ishikawa in a dose-dependent manner (P< 0.02 and P< 0.03, respectively). Rosiglitazone also induced apoptosis in both Hec-1-A (P< .001) and Ishikawa (P< .001) cells in a dose-dependent manner. In the murine model, rosiglitazone decreased proliferation of the endometrial hyperplastic lesions (B vs C; 39.7% vs 9.3% and B vs D; 39.7% vs 4.2%; P< 0.0001) and increased apoptosis of glandular endometrial epithelial cells (B vs C; 2.8% vs 22.4%; P< 0.0001 and B vs D; 2.8% vs 30.2%; P= 0.003). PPAR-γ agonist rosiglitazone inhibits proliferation and induces apoptosis in both PTEN intact and PTEN null cancer cell lines and in hyperplastic endometrial lesions in the PTEN+/− murine model.

scholarly journals Sodium Acetate Inhibit TGF-β1-Induced Activation of Hepatic Stellate Cells by Restoring AMPK or c-Jun Signaling

2021 ◽  
Vol 8 ◽  
Author(s):  
Weiwei Li ◽  
Mingjuan Deng ◽  
Jiahui Gong ◽  
Xiaoying Zhang ◽  
Shaoyang Ge ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Sodium Acetate ◽  
Cell Activation ◽  
Stellate Cells ◽  
Short Chain Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Ppar Γ ◽  
Tgf Β1

Short-chain fatty acids (SCFAs) are crucial gut microbial metabolites that play a major role in the occurrence and development of hepatic fibrosis (HF). However, the effect of SCFAs on hepatic stellate cells (HSCs), the major pro-fibrogenic cells, is yet undefined. In this study, the effects of three major SCFAs (acetate, propionate, and butyrate) were assessed on the activation of HSCs. LX2 cells were activated with TGF-β1 and treated with sodium acetate (NaA), sodium propionate (NaP), or sodium butyrate (NaB). SCFA treatment significantly reduced the protein levels of α-SMA and the phosphorylation of Smad2 and decreased the mRNA expression of Acta2/Col1a1/Fn in cells compared to the TGF-β1 treatment. Among the three SCFAs, NaA revealed the best efficacy at alleviating TGF-β1-induced LX2 cell activation. Additionally, acetate accumulated in the cells, and G protein-coupled receptor (GPR) 43 silencing did not have any impact on the inhibition of LX2 cell activation by NaA. These findings indicated that NaA enters into the cells to inhibit LX2 cell activation independent of GPR43. The results of phosphokinase array kit and Western blot indicated that NaA increased the AMP-activated protein kinase (AMPK) activation and reduced the phosphorylation of c-Jun in cultured LX2 cells, and siRNA-peroxisome proliferator-activated receptor (PPAR) -γ abolished the inhibitory effects of NaA against TGF-β1-induced LX2 cell activation. In conclusion, this study showed that NaA inhibited LX2 cell activation by activating the AMPK/PPARγ and blocking the c-Jun signaling pathways. Thus, SCFAs might represent a novel and viable approach for alleviating HF.

scholarly journals Andrographis paniculata and Its Main Bioactive Ingredient Andrographolide Decrease Alcohol Drinking and Seeking in Rats Through Activation of Nuclear PPARγ Pathway

2021 ◽  
Author(s):  
Serena Stopponi ◽  
Yannick Fotio ◽  
Carlo Cifani ◽  
Hongwu Li ◽  
Carolina L Haass-Koffler ◽  
...  
Keyword(s):  
Oral Administration ◽  
Alcohol Drinking ◽  
Andrographis Paniculata ◽  
Peroxisome Proliferator ◽  
Herbaceous Plant ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Treatment Administration ◽  
Dried Extract

Abstract Background and aims Andrographis paniculata is an annual herbaceous plant which belongs to the Acanthaceae family. Extracts from this plant have shown hepatoprotective, anti-inflammatory and antidiabetic properties, at least in part, through activation of the nuclear receptor Peroxisome Proliferator-Activated Receptor-gamma (PPAR γ). Recent evidence has demonstrated that activation of PPARγ reduces alcohol drinking and seeking in Marchigian Sardinian (msP) alcohol-preferring rats. Methods The present study evaluated whether A. paniculata reduces alcohol drinking and relapse in msP rats by activating PPARγ. Results Oral administration of an A. paniculata dried extract (0, 15, 150 mg/kg) lowered voluntary alcohol consumption in a dose-dependent manner and achieved ~65% reduction at the dose of 450 mg/kg. Water and food consumption were not affected by the treatment. Administration of Andrographolide (5 and 10 mg/kg), the main active component of A. paniculata, also reduced alcohol drinking. This effect was suppressed by the selective PPARγ antagonist GW9662. Subsequently, we showed that oral administration of A. paniculata (0, 150, 450 mg/kg) prevented yohimbine- but not cues-induced reinstatement of alcohol seeking. Conclusions Results point to A. paniculata-mediated PPARγactivation as a possible therapeutic strategy to treat alcohol use disorder.

scholarly journals Diet and PPARG2 Pro12Ala Polymorphism Interactions in Relation to Cancer Risk: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 261
Author(s):  
Lieu Tran ◽  
Gerd Bobe ◽  
Gayatri Arani ◽  
Yang Zhang ◽  
Zhenzhen Zhang ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Dietary Factors ◽  
Dietary Fats ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Allele Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Complex Relation ◽  
Ppar Γ ◽  
Pubmed Database

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.

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