Modeling the interaction between quinolinate and the receptor for advanced glycation end products (RAGE): Relevance for early neuropathological processes

Iris N. Serratos, Pilar Castellanos, Nina Pastor, César Millán-Pacheco, Daniel Rembao, Ruy Pérez-Montfort, Nallely Cabrera, Francisco Reyes-Espinosa, Paulina Díaz-Garrido, Ambar López-Macay, Karina Martínez-Flores, Alberto López-Reyes, Aurora Sánchez-García, Elvis Cuevas, Abel Santamaria

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11 Scopus citations

Abstract

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor involved in neurodegenerative and inflammatory disorders. RAGE induces cellular signaling upon binding to a variety of ligands. Evidence suggests that RAGE up-regulation is involved in quinolinate (QUIN)-induced toxicity.We investigated the QUIN-induced toxic events associated with early noxious responses, which might be linked to signaling cascades leading to cell death. The extent of early cellular damage caused by this receptor in the rat striatum was characterized by image processing methods. To document the direct interaction between QUIN and RAGE, we determined the binding constant (Kb) of RAGE (VC1 domain) with QUIN through a fluorescence assay. We modeled possible binding sites of QUIN to the VC1 domain for both rat and human RAGE. QUIN was found to bind at multiple sites to the VC1 dimer, each leading to particular mechanistic scenarios for the signaling evoked by QUIN binding, some of which directly alter RAGE oligomerization. This work contributes to the understanding of the phenomenon of RAGE-QUIN recognition, leading to the modulation of RAGE function.

Original languageEnglish
Article numbere0120221
JournalPLoS ONE
Volume10
Issue number3
DOIs
StatePublished - 10 Mar 2015
Externally publishedYes

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    Serratos, I. N., Castellanos, P., Pastor, N., Millán-Pacheco, C., Rembao, D., Pérez-Montfort, R., Cabrera, N., Reyes-Espinosa, F., Díaz-Garrido, P., López-Macay, A., Martínez-Flores, K., López-Reyes, A., Sánchez-García, A., Cuevas, E., & Santamaria, A. (2015). Modeling the interaction between quinolinate and the receptor for advanced glycation end products (RAGE): Relevance for early neuropathological processes. PLoS ONE, 10(3), [e0120221]. https://doi.org/10.1371/journal.pone.0120221