Linked Life Data

20722721

Source:http://linkedlifedata.com/resource/pubmed/id/20722721

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-11-5
pubmed:abstractText
Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is a key mediator of long-term potentiation (LTP), which can be triggered by N-methyl-d-aspartate (NMDA) receptor-mediated Ca(2+) influx. We previously demonstrated that Fyn kinase-mediated phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 in the dorsal horn was involved in a neuropathic pain state even 1 week after nerve injury. Here we show that Y1472F-KI mice with a knock-in mutation of the Tyr1472 site to phenylalanine did not exhibit neuropathic pain induced by L5 spinal nerve transection, whereas they did retain normal nociceptive responses and induction of inflammatory pain. Phosphorylation of NR2B at Tyr1472 was only impaired in the spinal cord of Y1472F-KI mice among the major phosphorylation sites. There was no difference in the Ca(2+) response to glutamate and sensitivity to NMDA receptor antagonists between naive wild-type and Y1472F-KI mice, and the Ca(2+) response to glutamate was attenuated in the Y1472F-KI mice after nerve injury. Autophosphorylation of CaMKII at Thr286 was markedly impaired in Y1472F-KI mice after nerve injury, but there was no difference in phosphorylation of CaMKII at Thr305 or protein kinase C? at Thr674, and activation of neuronal nitric oxide synthase and microglia in the superficial layer of spinal cord between wild-type and Y1472F-KI mice after the operation. These results demonstrate that the attenuation of neuropathic pain is caused by the impaired NMDA receptor-mediated CaMKII signaling in Y1472F-KI mice, and suggest that autophosphorylation of CaMKII at Thr286 plays a central part not only in LTP, but also in persistent neuropathic pain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1460-9568
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
798-810
pubmed:meshHeading
pubmed-meshheading:20722721-Animals, pubmed-meshheading:20722721-Calcium, pubmed-meshheading:20722721-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:20722721-Disease Models, Animal, pubmed-meshheading:20722721-Gene Knock-In Techniques, pubmed-meshheading:20722721-Glutamic Acid, pubmed-meshheading:20722721-Inflammation, pubmed-meshheading:20722721-Mice, pubmed-meshheading:20722721-Mice, Inbred C57BL, pubmed-meshheading:20722721-Models, Neurological, pubmed-meshheading:20722721-Neuralgia, pubmed-meshheading:20722721-Nitric Oxide Synthase Type I, pubmed-meshheading:20722721-Pain, pubmed-meshheading:20722721-Phosphorylation, pubmed-meshheading:20722721-Protein Kinase C, pubmed-meshheading:20722721-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:20722721-Signal Transduction, pubmed-meshheading:20722721-Spinal Cord, pubmed-meshheading:20722721-Spinal Nerves
pubmed:year
2010
pubmed:articleTitle
Impairment of CaMKII activation and attenuation of neuropathic pain in mice lacking NR2B phosphorylated at Tyr1472.
pubmed:affiliation
Department of Medical Chemistry, Kansai Medical University, Moriguchi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't