TY - JOUR
T1 - Modeling the interaction between quinolinate and the receptor for advanced glycation end products (RAGE)
T2 - Relevance for early neuropathological processes
AU - Serratos, Iris N.
AU - Castellanos, Pilar
AU - Pastor, Nina
AU - Millán-Pacheco, César
AU - Rembao, Daniel
AU - Pérez-Montfort, Ruy
AU - Cabrera, Nallely
AU - Reyes-Espinosa, Francisco
AU - Díaz-Garrido, Paulina
AU - López-Macay, Ambar
AU - Martínez-Flores, Karina
AU - López-Reyes, Alberto
AU - Sánchez-García, Aurora
AU - Cuevas, Elvis
AU - Santamaria, Abel
N1 - Publisher Copyright:
© 2015 Serratos et al.
PY - 2015/3/10
Y1 - 2015/3/10
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0120221
DO - 10.1371/journal.pone.0120221
M3 - Article
C2 - 25757085
AN - SCOPUS:84924371085
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 3
M1 - e0120221
ER -