Acute intrastriatal administration of quinolinic acid affects the expression of the coat protein AP-2 and its interaction with membranes.
Clathrin-coated vesicle endocytosis is thought to be crucial for the maintenance of synaptic transmission and for the cell plasticity at the nervous system. In this study, we demonstrated that acute intrastriatal administration of quinolinic acid (QUIN), an agonist of the N-methyl-D: -aspartate receptor, induces a decrease of the coat protein AP-2 expression and affects their interaction with membranes. By western blot analysis we observed that at 24 h after QUIN intrastriatal injection, alpha1 subunit of AP-2 and alpha2, at lesser extent, were reduced in the striatal membranes. The decrease of both subunits expression was extended to 48 h after treatment, although the soluble proteins were mostly affected. Other areas of the brain were not affected by the treatment, except the cerebellum, where a significant increase of soluble AP-2 (both subunits) was observed at 48 h after injection. Another coat protein, as the phosphoprotein AP-180, was not affected by the injection of QUIN. We also confirmed that QUIN injection causes increasing loss of striatal neurons after the administration of the toxin. We concluded that QUIN may affect the endocytotic machinery of the striatum, by inducing changes in the AP-2 behaviour. Consequently, the internalization of NMDAR and/or AMPAR may be affected, by QUIN, contributing to the excitotoxic effect of the drug.
Borgonovo
Janina
J
Laboratorio de Biología y Fisiología Celular Dr. Francisco Bertini, Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Seltzer
Alicia
A
Sosa
Miguel Angel
MA
D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000502:physiology; D008297:Male; D034041:Monomeric Clathrin Assembly Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D013997:Time Factors
D033962:Adaptor Protein Complex 2; D034041:Monomeric Clathrin Assembly Proteins; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; C439023:clathrin assembly protein AP180; D017378:Quinolinic Acid