Faculty Opinions recommendation of Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest.

2018 ◽  
Author(s):  
Ferdinando Boero ◽  
Stanislao Bevilacqua
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist

scholarly journals Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Combined Use

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.

scholarly journals Oxidized alkyl phospholipids stimulate sodium transport in proximal tubules via PPAR-dependent pathway

2021 ◽  
Author(s):  
Tomohito Mizuno ◽  
Nobuhiko Satoh ◽  
Shoko Horita ◽  
Hiroyuki Tsukada ◽  
Yusuke Sato ◽  
...  
Keyword(s):  
Volume Expansion ◽  
Bicarbonate Transport ◽  
Kidney Cortex ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal

The pleiotropic effects of oxidized phospholipids (oxPLs) have been identified. 1-O-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine (azPC), an oxPL formed from alkyl phosphatidylcholines, is a potent peroxisome proliferator-activated receptor (PPAR) agonist. Although it has been reported that thiazolidinediones can induce volume expansion by enhancing renal sodium and water retention, the role of azPC, an endogenous PPAR agonist, in renal transport functions is unknown. In the present study, we investigated the effect of azPC on renal proximal tubule (PT) transport using isolated PTs and kidney cortex tissues. We showed that azPC rapidly stimulated Na+/HCO3- cotransporter 1 activity and luminal Na+/H+ exchanger (NHE) activities in a dose-dependent manner, at submicromolar concentrations, in isolated PTs from rats and humans. Additionally, the stimulatory effects were completely blocked by a specific PPAR antagonist, 2-chloro-5-nitro-N-phenylbenzamide (GW9662), and a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor, PD98059. Treatment with an siRNA against PPAR significantly suppressed the expression of PPAR mRNA, and it completely blocked the stimulation of both Na+/HCO3- cotransporter 1 and NHE activities by azPC. Moreover, azPC induced extracellular signal-regulated kinase (ERK) phosphorylation in rat and human kidney cortex tissues, and the induced ERK phosphorylation by azPC was completely suppressed by GW9662 and PD98059. These results suggest that azPC stimulates renal PT sodium-coupled bicarbonate transport via the PPAR/MEK/ERK pathway. The stimulatory effects of azPC on PT transport may be partially involved in the development of volume expansion.

scholarly journals Effects of Selective Peroxisome Proliferator Activated Receptor Agonists on Corneal Epithelial Wound Healing

2021 ◽  
Vol 14 (2) ◽  
pp. 88
Author(s):  
Yutaro Tobita ◽  
Takeshi Arima ◽  
Yuji Nakano ◽  
Masaaki Uchiyama ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Vehicle Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Corneal Epithelial ◽  
Ppar Agonist ◽  
Alkali Burn ◽  
Epithelial Wound Healing ◽  
Epithelial Healing

The effects of each subtype-selective peroxisome proliferator activated receptor (PPAR) agonist (α, β/δ, γ) on corneal epithelial wound healing were investigated using a rat corneal alkali burn model. After the alkali burn, each PPAR agonist or vehicle ophthalmic solution was instilled topically onto the rat’s cornea. Corneal epithelial healing processes were evaluated by fluorescein staining. Pathological analyses and real-time reverse transcription polymerase chain reactions were performed to evaluate Ki67 (proliferative maker) expression and inflammatory findings. The area of the corneal epithelial defect at 12 h and 24 h after the alkali burn was significantly smaller in each PPAR group than in the vehicle group. Ki67 mRNA expression was increased in the PPARβ/δ group, whereas mRNA expressions of inflammatory cytokines were suppressed in all of the PPAR agonist groups. Nuclear factor kappa B (NF-κB) was the most suppressed in the PPARγ group. The accelerated corneal epithelial healing effects of each PPAR ligand were thought to be related to the promotion of proliferative capacity and inhibition of inflammation.

scholarly journals Hypoglycemic and Hypolipidemic Effects of a Novel Pan-Peroxisome Proliferator-Activated Receptor Agonist, MBT1805, in db/db Mices

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Wang C ◽  
◽  
Jin X ◽  
Jin Q ◽  
Shi Y ◽  
...  
Keyword(s):  
Weight Gain ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Hepatocyte Damage ◽  
In Vitro Transfection

Background: MBT1805 is a novel pan-Peroxisome Proliferator-Activated Receptor (PPAR) agonist. Materials and Methods: In vitro, transfection and luciferase assays tested EC50 values of MBT1805. In vivo, hypoglycemic and hypolipidemic effects of MBT1805 were observed in db/db mice compared with Rosiglitazone. Results: In vitro, MBT1805 activates human PPARα, PPARγ and PPARδ with EC50 values of 8.46μM, 11.94μM, 11.15μM, respectively. Results showed that the bodyweight of db/db mice treated with MBT1805 was not changed. By contrast, Rosiglitazone-treated mice showed significant weight gain (p<0.05). MTB1805 decreased blood glucose level without causing noticeable hepatocytes damage. Conclusion: The novel balanced pan-PPAR agonist, MBT1805 has moderate hypoglycemic and hypolipidemic effects, and does not cause weight gain, hepatocyte damage and hepatic lipid deposition. These experimental results indicate that MBT1805 is safe in the treatment of type 2 diabetes.

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