Early expression of the receptor for advanced glycation end products in a toxic model produced by 6-hydroxydopamine in the rat striatum

The receptor for advanced glycation end products (RAGE) is commonly involved in different neurodegenerative and inflammatory disorders. The cellular signaling associated to RAGE activation may occur upon binding to different ligands. In this study we investigated whether the toxic model produced by...

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Bibliographic Details
Published in:Chemico-biological interactions 2016-04, Vol.249, p.10-18
Main Authors: Serratos, Iris N., Castellanos, Pilar, Pastor, Nina, Millán-Pacheco, César, Colín-González, Ana Laura, Rembao, Daniel, Pérez-Montfort, Ruy, Cabrera, Nallely, Sánchez-García, Aurora, Gómez, Isabel, Rangel-López, Edgar, Santamaria, Abel
Format: Article
Language:English
Subjects:
6-Hydroxydopamine
AGES
Animals
Binding constant
Binding Sites - physiology
Corpus Striatum - metabolism
Docking
Ligands
Male
Neurotoxicity
Oxidopamine - metabolism
Protein Binding - physiology
RAGE expression
Rats
Rats, Wistar
Receptor for Advanced Glycation End Products - metabolism
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Summary:The receptor for advanced glycation end products (RAGE) is commonly involved in different neurodegenerative and inflammatory disorders. The cellular signaling associated to RAGE activation may occur upon binding to different ligands. In this study we investigated whether the toxic model produced by 6-hydroxydopamine (6-OHDA) in rats comprises early noxious responses related to RAGE-mediated signaling cascades. In order to explore a possible interaction between 6-OHDA and RAGE, affinity parameters of RAGE with 6-OHDA were estimated by different means. The possible binding sites of 6-OHDA with the VC1 homodimer for both rat and human RAGE were also modeled. Our results show that the striatal infusion of 6-OHDA recruits RAGE upregulation, as evidenced by an early expression of the receptor. 6-OHDA was also found to bind the VC1 homodimer, although its affinity was moderate when compared to other ligands. This work contributes to the understanding of the role of RAGE activation for 6-OHDA-induced neurotoxicity. •6-OHDA upregulates RAGE in the rat striatum.•RAGE upregulation occurs during the first stages of 6-OHDA toxicity.•6-OHDA possesses moderate affinity for RAGE protein.
ISSN:0009-2797
1872-7786
DOI:10.1016/j.cbi.2016.02.014