scholarly journals PPAR Agonist-Mediated Protection against HIV Tat-Induced Cerebrovascular Toxicity is Enhanced in MMP-9-Deficient Mice

2014 ◽  
Vol 34 (4) ◽  
pp. 646-653 ◽  
Author(s):  
Wen Huang ◽  
Lei Chen ◽  
Bei Zhang ◽  
Minseon Park ◽  
Michal Toborek
Keyword(s):  
Neuronal Loss ◽  
Specific Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brain Infection ◽  
Ppar Γ ◽  
Ppar Agonists ◽  
Bbb Permeability ◽  
Deficient Mice ◽  
Hiv 1

The strategies to protect against the disrupted blood–brain barrier (BBB) in HIV-1 infection are not well developed. Therefore, we investigated the potential of peroxisome proliferator-activated receptor (PPAR) agonists to prevent enhanced BBB permeability induced by HIV-1-specific protein Tat. Exposure to Tat via the internal carotid artery (ICA) disrupted permeability across the BBB; however, this effect was attenuated in mice treated with fenofibrate (PPAR α agonist) or rosiglitazone (PPAR γ agonist). In contrast, exposure to GW9662 (PPAR γ antagonist) exacerbated Tat-induced disruption of the BBB integrity. Increased BBB permeability was associated with decreased tight junction (TJ) protein expression and activation of ERK1/2 and Akt in brain microvessels; these effects were attenuated by cotreatment with fenofibrate but not with rosiglitazone. Importantly, both PPAR agonists also protected against Tat-induced astrogliosis and neuronal loss. Because disruption of TJ integrity has been linked to matrix metalloproteinase (MMP) activity, we also evaluated Tat-induced effects in MMP-9-deficient mice. Tat-induced cerebrovascular toxicity, astrogliosis, and neuronal loss were less pronounced in MMP-9-deficient mice as compared with wild-type controls and were further attenuated by PPAR agonists. These results indicate that enhancing PPAR activity combined with targeting MMPs may provide effective therapeutic strategies in brain infection by HIV-1.

scholarly journals Sex dimorphic actions of rosiglitazone in generalised peroxisome proliferator-activated receptor-γ (PPAR-γ)-deficient mice

Diabetologia ◽  
2010 ◽  
Vol 53 (7) ◽  
pp. 1493-1505 ◽  
Author(s):  
S. Z. Duan ◽  
M. G. Usher ◽  
E. L. Foley ◽  
D. S. Milstone ◽  
F. C. Brosius ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Deficient Mice

scholarly journals Erratum to: Sex dimorphic actions of rosiglitazone in generalised peroxisome proliferator-activated receptor-γ (PPAR-γ)-deficient mice

Diabetologia ◽  
2011 ◽  
Vol 55 (1) ◽  
pp. 270-271
Author(s):  
S. Z. Duan ◽  
M. G. Usher ◽  
E. L. Foley ◽  
D. S. Milstone ◽  
F. C. Brosius ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Deficient Mice

Ciglitazone Inhibits Plasmin-Induced Proinflammatory Monocyte Activation via Modulation of p38 MAP Kinase Activity

2002 ◽  
Vol 88 (08) ◽  
pp. 274-281 ◽  
Author(s):  
Tatiana Syrovets ◽  
Almut Schüle ◽  
Marina Jendrach ◽  
Berthold Büchele ◽  
Thomas Simmet
Keyword(s):  
Gene Activation ◽  
P38 Map Kinase ◽  
Clofibric Acid ◽  
Peroxisome Proliferator ◽  
Surface Plasmon Resonance Analysis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Pparγ Agonist ◽  
Tnf Α ◽  
Ppar Agonists

SummaryPlasmin triggers chemotaxis and NF-κBand AP-1-mediated proinflammatory gene expression in human peripheral monocytes (PM). Compared with macrophages and dendritic cells, PM express mainly the peroxisome proliferator-activated receptor (PPAR) γ and traces of PPARα as detected by semiquantitative RT-PCR and immunoblotting. The PPARγ agonist ciglitazone, but not the PPARα agonist clofibric acid, concentration-dependently inhibited the plasmin-, but not the FMLP-induced PM chemotaxis. Similarly, release of interleukin (IL)-1α, IL-1β and tumor necrosis factor (TNF)-α from plasmin-stimulated PM was concentration-dependently inhibited by ciglitazone, but not by clofibric acid, while the LPS-induced TNF-α release remained unaffected by any of both PPAR agonists. Ciglitazone activates PPARγ as shown by a novel surface plasmon resonance analysis and inhibits the plasmin-induced activation of NF-κB and AP-1. It also inhibits p38 MAPK phosphorylation essential for the plasmin-induced PM chemotaxis and gene activation. Thus, activation of PPARγ by ciglitazone may allow controling of the plasmin-mediated recruitment and activation of PM at sites of inflammation.

Mechanism of constrictive vascular remodeling by homocysteine: role of PPAR

2002 ◽  
Vol 282 (5) ◽  
pp. C1009-C1015 ◽  
Author(s):  
Vibhas S. Mujumdar ◽  
Chandra M. Tummalapalli ◽  
Giorgio M. Aru ◽  
Suresh C. Tyagi
Keyword(s):  
Endothelial Cells ◽  
Vascular Remodeling ◽  
Peroxisome Proliferator ◽  
Collagen Gels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Aortic Endothelial Cells ◽  
Ppar Γ ◽  
Collagen Contraction ◽  
Ppar Agonists

To test the hypothesis that homocysteine induces constrictive vascular remodeling by inactivating peroxisome proliferator-activated receptor (PPAR), aortic endothelial cells (ECs) and smooth muscle cells (SMCs) were isolated. Collagen gels were prepared, and ECs or SMCs (105) or SMCs + ECs (104) were incorporated into the gels. To characterize PPAR, agonists of PPAR-α [ciprofibrate (CF)] and PPAR-γ [15-deoxy-12,14-prostaglandin J2 (PGJ2)] were used. To determine the role of disintegrin metalloproteinase (DMP), cardiac inhibitor of metalloproteinase (CIMP) was used in collagen gels. Gel diameter at 0 h was 14.1 ± 0.2 mm and was unchanged up to 24 h as measured by a digital micrometer. SMCs reduce gel diameter to 10.5 ± 0.4 mm at 24 h. Addition of homocysteine to SMCs reduces further the gel diameter to 8.0 ± 0.2 mm, suggesting that SMCs induce contraction and that the contraction is further enhanced by homocysteine. Addition of ECs and SMCs reduces gel diameter to 12.0 ± 0.3 mm, suggesting that ECs play a role in collagen contraction. Only PGJ2, not CF, inhibits SMC contraction. However, both PGJ2 and CF inhibit contraction of ECs and SMCs + ECs. Addition of anti-DMP blocks SMC- as well as homocysteine-mediated contraction. However, CIMP inhibits only homocysteine-mediated contraction. The results suggest that homocysteine may enhance vascular constrictive remodeling by inactivating PPAR-α and -γ in ECs and PPAR-γ in SMCs.

scholarly journals PPAR-γ Agonists and Their Role in Primary Cicatricial Alopecia

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Sarawin Harnchoowong ◽  
Poonkiat Suchonwanit
Keyword(s):  
Clinical Trials ◽  
Review Article ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Biogenesis ◽  
Sebaceous Glands ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lichen Planopilaris ◽  
Ppar Γ ◽  
Ppar Agonists

Peroxisome proliferator-activated receptor γ (PPAR-γ) is a ligand-activated nuclear receptor that regulates the transcription of various genes. PPAR-γ plays roles in lipid homeostasis, sebocyte maturation, and peroxisome biogenesis and has shown anti-inflammatory effects. PPAR-γ is highly expressed in human sebaceous glands. Disruption of PPAR-γ is believed to be one of the mechanisms of primary cicatricial alopecia (PCA) pathogenesis, causing pilosebaceous dysfunction leading to follicular inflammation. In this review article, we discuss the pathogenesis of PCA with a focus on PPAR-γ involvement in pathogenesis of lichen planopilaris (LPP), the most common lymphocytic form of PCA. We also discuss clinical trials utilizing PPAR-agonists in PCA treatment.

scholarly journals Adipocyte-Specific ACKR3 Regulates Lipid Levels in Adipose Tissue

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 394
Author(s):  
Selin Gencer ◽  
Yvonne Döring ◽  
Yvonne Jansen ◽  
Soyolmaa Bayasgalan ◽  
Olga Schengel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Cholesterol Content ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Lipid Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Deficient Mice

Dysfunctional adipose tissue (AT) may contribute to the pathology of several metabolic diseases through altered lipid metabolism, insulin resistance, and inflammation. Atypical chemokine receptor 3 (ACKR3) expression was shown to increase in AT during obesity, and its ubiquitous elimination caused hyperlipidemia in mice. Although these findings point towards a role of ACKR3 in the regulation of lipid levels, the role of adipocyte-specific ACKR3 has not yet been studied exclusively in this context. In this study, we established adipocyte- and hepatocyte-specific knockouts of Ackr3 in ApoE-deficient mice in order to determine its impact on lipid levels under hyperlipidemic conditions. We show for the first time that adipocyte-specific deletion of Ackr3 results in reduced AT triglyceride and cholesterol content in ApoE-deficient mice, which coincides with increased peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased Angptl4 expression. The role of adipocyte ACKR3 in lipid handling seems to be tissue-specific as hepatocyte ACKR3 deficiency did not demonstrate comparable effects. In summary, adipocyte-specific ACKR3 seems to regulate AT lipid levels in hyperlipidemic Apoe−/− mice, which may therefore be a significant determinant of AT health. Further studies are needed to explore the potential systemic or metabolic effects that adipocyte ACKR3 might have in associated disease models.

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.

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