Linked Life Data

17492691

Source:http://linkedlifedata.com/resource/pubmed/id/17492691

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-6-25
pubmed:abstractText
Previous studies have shown that subtoxic NMDA moderated the neuronal survival in vitro and vivo. We performed this experiment to clarify the precise mechanism underlie subtoxic NMDA delayed neuronal death in ischemic brain injury. We found that pretreatment of NMDA (100 mg/kg) increased the number of the surviving CA1 pyramidal cells of hippocampus at 5 days of reperfusion. This dose of NMDA could also enhance Akt activation after ischemia/reperfusion (I/R). Here, we examined the possible mechanism that NMDA induced Akt activation. On the one hand, we found NMDA receptor-mediated Akt activation was associated with increased expression of BDNF (brain-derived neurotrophic factor) and activation of its high-affinity receptor TrkB after I/R in the hippocampus CA1 region, which could be held down by TrkB receptor antagonist K252a. On the other hand, we found that NMDA enhanced the binding of Ca2+-dependent calmodulin (CaM) to p85 (the regulation subunit of PI-3K), which led to the activation of Akt. W-13, an active CaM inhibitor, prevented the combination of CaM and p85 and subsequent Akt activation. Furthermore, NMDA receptor-mediated Akt activation was reversed by combined treatment with LY294002, the specific blockade of PI-3K. Taken together, our results suggested that subtoxic NMDA exerts the neuroprotective effect via activation of prosurvival PI-3K/Akt pathway against ischemic brain injury, and BDNF-TrkB signaling and Ca2+-dependent CaM cascade might contribute to NMDA induced activation of PI-3K/Akt pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1050-9631
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
525-37
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17492691-Animals, pubmed-meshheading:17492691-Brain Infarction, pubmed-meshheading:17492691-Brain Ischemia, pubmed-meshheading:17492691-Brain-Derived Neurotrophic Factor, pubmed-meshheading:17492691-Calcium Signaling, pubmed-meshheading:17492691-Calmodulin, pubmed-meshheading:17492691-Cell Survival, pubmed-meshheading:17492691-Enzyme Activation, pubmed-meshheading:17492691-Enzyme Inhibitors, pubmed-meshheading:17492691-Hippocampus, pubmed-meshheading:17492691-Male, pubmed-meshheading:17492691-N-Methylaspartate, pubmed-meshheading:17492691-Nerve Degeneration, pubmed-meshheading:17492691-Neuroprotective Agents, pubmed-meshheading:17492691-Phosphatidylinositol 3-Kinases, pubmed-meshheading:17492691-Protein Subunits, pubmed-meshheading:17492691-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17492691-Pyramidal Cells, pubmed-meshheading:17492691-Rats, pubmed-meshheading:17492691-Rats, Sprague-Dawley, pubmed-meshheading:17492691-Receptor, trkB, pubmed-meshheading:17492691-Reperfusion Injury, pubmed-meshheading:17492691-Signal Transduction
pubmed:year
2007
pubmed:articleTitle
Subtoxic N-methyl-D-aspartate delayed neuronal death in ischemic brain injury through TrkB receptor- and calmodulin-mediated PI-3K/Akt pathway activation.
pubmed:affiliation
Research Center for Biochemistry and Molecular Biology, The Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Jiangsu, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't