Dataset Information

Functional N-Formyl Peptide Receptor?2 (FPR2) Antagonists Based on the Ureidopropanamide Scaffold Have Potential To Protect Against Inflammation-Associated Oxidative Stress.

ABSTRACT: Formyl peptide receptor?2 (FPR2) is a G protein coupled receptor belonging to the N-formyl peptide receptor (FPR) family that plays critical roles in peripheral and brain inflammatory responses. FPR2 has been proposed as a target for the development of drugs that could facilitate the resolution of chronic inflammatory reactions by enhancing endogenous anti-inflammation systems. Starting from lead compounds previously identified in our laboratories, we designed a new series of ureidopropanamide derivatives with the goal of converting functional activity from agonism into antagonism and to develop new FPR2 antagonists. Although none of the compounds behaved as antagonists, some of the compounds were able to induce receptor desensitization and, thus, functionally behaved as antagonists. Evaluation of these compounds in an in?vitro model of neuroinflammation showed that they decreased the production of reactive oxygen species in mouse microglial N9 cells after stimulation with lipopolysaccharide. These FPR2 ligands may protect cells from damage due to inflammation-associated oxidative stress.

SUBMITTER: Stama ML

PROVIDER: S-EPMC5909973 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional N-Formyl Peptide Receptor 2 (FPR2) Antagonists Based on the Ureidopropanamide Scaffold Have Potential To Protect Against Inflammation-Associated Oxidative Stress.

Stama Madia L ML Lacivita Enza E Kirpotina Liliya N LN Niso Mauro M Perrone Roberto R Schepetkin Igor A IA Quinn Mark T MT Leopoldo Marcello M

ChemMedChem 20171107 22

Formyl peptide receptor 2 (FPR2) is a G protein coupled receptor belonging to the N-formyl peptide receptor (FPR) family that plays critical roles in peripheral and brain inflammatory responses. FPR2 has been proposed as a target for the development of drugs that could facilitate the resolution of chronic inflammatory reactions by enhancing endogenous anti-inflammation systems. Starting from lead compounds previously identified in our laboratories, we designed a new series of ureidopropanamide d ...[more]

PMID: 28922577

Similar Datasets

Project description:BackgroundMyocardial injury is the main manifestation of cardiovascular diseases, and previous studies have shown that propofol (PPF) regulates myocardial injury. However, the mechanism of PPF in regulating myocardial injury remains to be further explored. This work aims to analyze the effects of PPF on human cardiomyocyte injury and the underlying mechanism.MethodsThe regulatory and functional role of PPF and circAPBB2 in human cardiomyocyte injury were analyzed using an in vitro hypoxia/reoxygenation (H/R) cell model, which was established by treating human cardiomyocytes (AC16 cells) with H/R. The study evaluated AC16 cell injury by analyzing cytotoxicity, oxidative stress, inflammation and apoptosis of H/R-induced AC16 cells. Quantitative real-time polymerase chain reaction was performed to detect circAPBB2, miR-18a-5p and dual specificity phosphatase 14 (DUSP14) expression. Protein expression was analyzed by Western blot analysis assay. Dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay were performed to identify the associations among circAPBB2, miR-18a-5p and DUSP14. Cytotoxicity was investigated by cell counting kit-8 assay and lactate dehydrogenase activity detection kit. Oxidative stress was evaluated by cellular reactive oxygen species assay kit and superoxide dismutase activity assay kit. The production of tumor necrosis factor-α and interleukin-1β was evaluated by enzyme-linked immunosorbent assays.ResultsThe expression of circAPBB2 and DUSP14 was significantly decreased, while miR-18a-5p was increased in H/R-induced AC16 cells when compared with controls. H/R treatment-induced cytotoxicity, oxidative stress, inflammation and cell apoptosis were attenuated after circAPBB2 overexpression or PPF treatment, whereas these effects were restored by increasing miR-18a-5p expression. PPF treatment improved the inhibitory effect of ectopic circAPBB2 expression on H/R-induced cell injury. MiR-18a-5p silencing ameliorated H/R-induced AC16 damage by interacting with DUSP14. Mechanically, circAPBB2 acted as a miR-18a-5p sponge, and miR-18a-5p targeted DUSP14 in AC16 cells.ConclusionPPF synergized with circAPBB2 to protect AC16 cells against H/R-induced oxidative stress, inflammation and apoptosis through the miR-18a-5p/DUSP14 pathway.

Dataset Information

Functional N-Formyl Peptide Receptor?2 (FPR2) Antagonists Based on the Ureidopropanamide Scaffold Have Potential To Protect Against Inflammation-Associated Oxidative Stress.

Publications

Functional N-Formyl Peptide Receptor 2 (FPR2) Antagonists Based on the Ureidopropanamide Scaffold Have Potential To Protect Against Inflammation-Associated Oxidative Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets