Title :

Development of an in vivo model for screening receptor for advanced glycation end products (RAGE) antagonists

Author(s) :

Dubois, Constance []
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
PAUL-CONSTANT, Charles [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Schmidt, Ann [Auteur]
New York University School of Medicine [NYU]
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Boulanger, Éric [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Fradin, Chantal [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]

Conference title :

Drug Discovery Day

City :

Lille

Country :

France

Start date of the conference :

2019-12-17

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Introduction : The impact of advanced glycation end-products (AGEs) on health has been widely studied. The structural and functional protein modifications induced by glycation are involved in the complications of many ...
Show more >Introduction : The impact of advanced glycation end-products (AGEs) on health has been widely studied. The structural and functional protein modifications induced by glycation are involved in the complications of many pathologies, such as diabetes. AGEs can also activate the AGE receptor (RAGE), initiating inflammation and oxidation that favor RAGE expression and AGEs formation. Recent studies have demonstrated the involvement of RAGE in the aging processes. The AGE-RAGE axis represents a promising therapeutic target to reduce the complications of different pathologies and to control both pathological and physiological aging. We decided to develop an in vivo screening system for RAGE antagonists using the aging study model Caenorhabditis elegans.Methods : The wild-type strain of C. elegans was transfected with the full-length human RAGE encoding gene, AGER. Control worms were transfected with either the gene coding for the green fluorescent protein (GFP) or the AGER gene missing the sequence coding for the cytoplasmic domain of RAGE. Both genes were driven by a worm promoter allowing their expression in the intestine. The longevity of the different transfected strains was measured in medium containing or not AGEs.Results : We successfully generated C. elegans strains that express either GFP or human RAGE (full-length or truncated receptor) in the intestine. The AGEs-rich diet reduced the lifespan of C. elegans which didn’t express RAGE (control GFP strain). The lifespan’s reduction was amplified for worms that expressed full-length human RAGE while it was attenuated in worms that expressed truncated RAGE, suggesting that human RAGE is activated by AGEs in C. elegans. Conclusion and future works : Our data show that expression of human RAGE determined C. elegans’ longevity on an AGEs-rich medium. We will use this model to study in vivo modulation of oxygen reactive species (ROS) generation by RAGE antagonists and their impact on the worms’ longevity. As C. elegans is transparent, non-invasive in vivo methods will be used to detect fluorescent molecules and a transgenic fluorescent reporter that offers the possibility to measure rates of both ROS generation and ROS scavenging by antioxidant systems.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL