Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia
Activation of the N-methyl-D-aspartate receptor (NMDAR) is fundamental in the development of hyperalgesia. Overactivation of this receptor releases superoxide and nitric oxide that, in turn, forms peroxynitrite (PN). All of these events have been linked to neurotoxicity. The receptors and enzymes in...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/950947 |
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| author | Carolina Muscoli Concetta Dagostino Sara Ilari Filomena Lauro Micaela Gliozzi Erlisa Bardhi Ernesto Palma Vincenzo Mollace Daniela Salvemini |
| author_facet | Carolina Muscoli Concetta Dagostino Sara Ilari Filomena Lauro Micaela Gliozzi Erlisa Bardhi Ernesto Palma Vincenzo Mollace Daniela Salvemini |
| author_sort | Carolina Muscoli |
| collection | DOAJ |
| description | Activation of the N-methyl-D-aspartate receptor (NMDAR) is fundamental in the development of hyperalgesia. Overactivation of this receptor releases superoxide and nitric oxide that, in turn, forms peroxynitrite (PN). All of these events have been linked to neurotoxicity. The receptors and enzymes involved in the handling of glutamate pathway—specifically NMDARs, glutamate transporter, and glutamine synthase (GS)—have key tyrosine residues which are targets of the nitration process causing subsequent function modification. Our results demonstrate that the thermal hyperalgesia induced by intrathecal administration of NMDA is associated with spinal nitration of GluN1 and GluN2B receptor subunits, GS, that normally convert glutamate into nontoxic glutamine, and glutamate transporter GLT1. Intrathecal injection of PN decomposition catalyst FeTM-4-PyP5+ prevents nitration and overall inhibits NMDA-mediated thermal hyperalgesia. Our study supports the hypothesis that nitration of key proteins involved in the regulation of glutamate transmission is a crucial pathway used by PN to mediate the development and maintenance of NMDA-mediated thermal hyperalgesia. The broader implication of our findings reinforces the notion that free radicals may contribute to various forms of pain events and the importance of the development of new pharmacological tool that can modulate the glutamate transmission without blocking its actions directly. |
| format | Article |
| id | doaj-art-992dedd843604eb596a04b46f9615d35 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-992dedd843604eb596a04b46f9615d352025-02-03T01:32:01ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/950947950947Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal HyperalgesiaCarolina Muscoli0Concetta Dagostino1Sara Ilari2Filomena Lauro3Micaela Gliozzi4Erlisa Bardhi5Ernesto Palma6Vincenzo Mollace7Daniela Salvemini8Department of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDrug Center, IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00163 Roma, ItalyDepartment of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDepartment of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDepartment of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDepartment of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDepartment of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDepartment of Health Sciences, University “Magna Graecia”, Edificio Bioscienze, Viale Europa, Campus Salvatore Venuta, Germaneto, 88100 Catanzaro, ItalyDepartment of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USAActivation of the N-methyl-D-aspartate receptor (NMDAR) is fundamental in the development of hyperalgesia. Overactivation of this receptor releases superoxide and nitric oxide that, in turn, forms peroxynitrite (PN). All of these events have been linked to neurotoxicity. The receptors and enzymes involved in the handling of glutamate pathway—specifically NMDARs, glutamate transporter, and glutamine synthase (GS)—have key tyrosine residues which are targets of the nitration process causing subsequent function modification. Our results demonstrate that the thermal hyperalgesia induced by intrathecal administration of NMDA is associated with spinal nitration of GluN1 and GluN2B receptor subunits, GS, that normally convert glutamate into nontoxic glutamine, and glutamate transporter GLT1. Intrathecal injection of PN decomposition catalyst FeTM-4-PyP5+ prevents nitration and overall inhibits NMDA-mediated thermal hyperalgesia. Our study supports the hypothesis that nitration of key proteins involved in the regulation of glutamate transmission is a crucial pathway used by PN to mediate the development and maintenance of NMDA-mediated thermal hyperalgesia. The broader implication of our findings reinforces the notion that free radicals may contribute to various forms of pain events and the importance of the development of new pharmacological tool that can modulate the glutamate transmission without blocking its actions directly.http://dx.doi.org/10.1155/2013/950947 |
| spellingShingle | Carolina Muscoli Concetta Dagostino Sara Ilari Filomena Lauro Micaela Gliozzi Erlisa Bardhi Ernesto Palma Vincenzo Mollace Daniela Salvemini Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia Mediators of Inflammation |
| title | Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia |
| title_full | Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia |
| title_fullStr | Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia |
| title_full_unstemmed | Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia |
| title_short | Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia |
| title_sort | posttranslational nitration of tyrosine residues modulates glutamate transmission and contributes to n methyl d aspartate mediated thermal hyperalgesia |
| url | http://dx.doi.org/10.1155/2013/950947 |
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