On the early toxic effect of quinolinic acid: involvement of RAGE

• Published in: Neuroscience letters Vol. 474; no. 2; pp. 74 - 78
• Main Authors: Cuevas, Elvis, Lantz, Susan, Newport, Glenn, Divine, Becky, Wu, Qiangen, Paule, Merle G, Tobón-Velasco, J César, Ali, Syed F, Santamaría, Abel
• Format: Journal Article
• Language: English
• Published: Ireland 26.04.2010
• Subjects: Animals; Condensation; Corpus Striatum - cytology; Corpus Striatum - drug effects; Cyclooxygenase 2 - metabolism; Gene Expression Regulation - drug effects; Glial Fibrillary Acidic Protein - metabolism; Indoles; L-Lactate Dehydrogenase - metabolism; Male; Neurotoxins - toxicity; NF-kappaB-Inducing Kinase; Nitrates - metabolism; Protein Serine-Threonine Kinases - metabolism; Quinolinic Acid - toxicity; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Spectrophotometry - methods; Superoxide Dismutase - metabolism
• ISSN: 1872-7972; 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.03.007

Quinolinic acid (QUIN)-induced toxicity is characterized by N-methyl-d-aspartate receptors over-activation, excitotoxicity and oxidative damage. The characterization of toxic cascades produced by QUIN during the first hours after its striatal infusion is relevant for understanding toxic mechanisms. The role of the receptor-for-advanced-glycation-end-products (RAGE) in the early toxic pattern induced by QUIN was evaluated. RAGE expression - assessed by Western blot analysis and immunofluorescence - was enhanced in the striata of QUIN-lesioned rats at 2h post-lesion. QUIN-induced RAGE up-regulation was accompanied by expression of a RAGE target molecule, nuclear factor kappa B (NF-kappaB), and genes encoding for different enzymes. Other toxic markers linked to RAGE activation were increased by QUIN, including NO formation, premature glial response, lactate dehydrogenase leakage, mitochondrial dysfunction and nuclear condensation. Our results suggest that RAGE up-regulation may play a role in the early stages of QUIN toxicity.