title: Modeling the interaction between quinolinate and the receptor for advanced glycation end products (RAGE): relevance for early neuropathological processes.
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.
authors.affiliation: Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, México D.F., México; Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, SSA, México D.F., México.
authors.forename: Iris N
authors.initials: IN
authors.lastname: Serratos
authors.affiliation: Departamento de Ingeniería Eléctrica, Universidad Autónoma Metropolitana-Iztapalapa, México D.F., México.
authors.forename: Pilar
authors.initials: P
authors.lastname: Castellanos
authors.affiliation: Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
authors.forename: Nina
authors.initials: N
authors.lastname: Pastor
authors.affiliation: Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
authors.forename: César
authors.initials: C
authors.lastname: Millán-Pacheco
authors.affiliation: Neuropatología, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, México D.F., México.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rembao
authors.affiliation: Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Ruy
authors.initials: R
authors.lastname: Pérez-Montfort
authors.affiliation: Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Nallely
authors.initials: N
authors.lastname: Cabrera
authors.affiliation: Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, México D.F., México.
authors.forename: Francisco
authors.initials: F
authors.lastname: Reyes-Espinosa
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, SSA, México D.F., México.
authors.forename: Paulina
authors.initials: P
authors.lastname: Díaz-Garrido
authors.affiliation: Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación, SSA, México D.F., México.
authors.forename: Ambar
authors.initials: A
authors.lastname: López-Macay
authors.affiliation: Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación, SSA, México D.F., México.
authors.forename: Karina
authors.initials: K
authors.lastname: Martínez-Flores
authors.affiliation: Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación, SSA, México D.F., México.
authors.forename: Alberto
authors.initials: A
authors.lastname: López-Reyes
authors.affiliation: Neuropatología, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, México D.F., México.
authors.forename: Aurora
authors.initials: A
authors.lastname: Sánchez-García
authors.affiliation: Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, Arkansas, United States of America.
authors.forename: Elvis
authors.initials: E
authors.lastname: Cuevas
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, SSA, México D.F., México.
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaria
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D008297:Male; D062105:Molecular Docking Simulation; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011485:Protein Binding; D017378:Quinolinic Acid / Q000737:chemistry* / Q000502:physiology; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000737:chemistry* / Q000378:metabolism
chemical_list: C000593874:Ager protein, rat; D000067759:Receptor for Advanced Glycation End Products; D017378:Quinolinic Acid