Quinolinic Acid Modulates the Activity of Src Family Kinases in Rat Striatum: in Vivo and in Vitro Studies.
From: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Rome, Italy.
Journal of neurochemistry
- Publish Date: Jun 2006
- ISSN: 0022-3042
- Volume: 97
- Issue: 5
- Pages: 1327-36
- Medium: Print
- Language: English
- Citation (JAMA): Metere Alessio, Mallozzi Cinzia, Minetti Maurizio, et al. Quinolinic Acid Modulates the Activity of Src Family Kinases in Rat Striatum: in Vivo and in Vitro Studies.. J. Neurochem. Jun 2006;97:1327-36
Abstract
Quinolinic acid (QA) has been shown to evoke neurotoxic events via NMDA receptor (NMDAR) overactivation and oxidative stress. NMDARs are particularly vulnerable to free radicals, which can modulate protein tyrosine kinase (PTK) and phosphotyrosine phosphatase (PTP) activities. The src family of tyrosine kinases are associated with the NMDAR complex and regulate NMDA channel function. Because QA is an NMDAR agonist as well as a pro-oxidant agent, we investigated whether it may affect the activity of PTKs and PTPs in vivo and in vitro. In synaptosomes prepared from striata dissected 15 min, 30 min or 15 days after bilateral injection of QA we observed modulation of the phosphotyrosine pattern; a significant decrease in PTP activity; and a sustained increase in c-src and lyn activity at 15 and 30 min after treatment with QA, followed by a decrease 2 weeks later. Striatal synaptosomes treated in vitro with QA showed time- and dose-dependent modulation of c-src and lyn kinase activities. Moreover, the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester, the NMDAR antagonist d-2-amino-5-phosphonovaleric acid and pyruvate suppressed the QA-induced modulation of c-src activity. These findings suggest a novel feature of QA in regulating src kinase activity through the formation of reactive radical species and/or NMDAR overactivation.
Mesh Headings (Keywords): Animals, Corpus Striatum, Dose-Response Relationship, Drug, Down-Regulation, Enzyme Activation, Excitatory Amino Acid Antagonists, Free Radicals, Huntington Disease, Male, Neurotoxins, Nitric Oxide Synthase, Oxidative Stress, Presynaptic Terminals, Protein Tyrosine Phosphatases, Protein-Tyrosine Kinases, Pyruvic Acid, Quinolinic Acid, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate, Synaptosomes, Time Factors, src-Family Kinases
Check for Full Text / PubMed Unique Identifier (PMID): 16638020
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