Linked Life Data

9843151

Source:http://linkedlifedata.com/resource/pubmed/id/9843151

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-3-11
pubmed:abstractText
MS-818 (2-piperadino-6-methyl-5-oxo-5, 6-dihydro (7H) pyrrolo [2,3-d]pyrimidine maleate), a newly synthesized heterocyclic pyrimidine derivative, promotes neurite outgrowth in neuronal cell lines. The survival-promoting effect of MS-818 on cultured neurons isolated from mouse cortices was examined. MS-818 promoted neuronal survival by inhibiting apoptosis in a dose-dependent manner. MS-818 treatment also activated mitogen-activated protein kinase (MAPK) of the extracellular signal regulation kinase 2, as demonstrated by Western blot analysis. The MAPK activation level in the cultures treated with MS-818 was almost equivalent to that in cultures treated with nerve growth factor but was less than that in cultures treated with epidermal growth factor and basic fibroblast growth factor (bFGF). MAPK was activated within 3 min after the addition of MS-818, and its activity level returned to baseline within 120 min. Its activation was protein kinase C independent. We further investigated the effect of concurrent treatment with MS-818 and bFGF on neuronal survival. MS-818 enhanced the neuronal survival-promoting effect of bFGF in shifting the half-maximally effective dose from 2.1 ng/ml to 0.036 ng/ml in the sigmoidal dose effect of bFGF and permitted nearly maximum MAPK activation. The enhancement by MS-818 of the neuronal survival-promoting effect of bFGF was accompanied by sustained activation of MAPK to a degree that far exceeded, in magnitude and duration, the cooperative effect of MS-818 and bFGF. These results indicate that MS-818 promotes neuronal survival and enhances the neurotrophic actions of bFGF through stimulation of synchronous signals that may elevate MAPK levels within neurons.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
604-12
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9843151-Animals, pubmed-meshheading:9843151-Apoptosis, pubmed-meshheading:9843151-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:9843151-Cells, Cultured, pubmed-meshheading:9843151-Cerebral Cortex, pubmed-meshheading:9843151-Depression, Chemical, pubmed-meshheading:9843151-Drug Synergism, pubmed-meshheading:9843151-Enzyme Activation, pubmed-meshheading:9843151-Fibroblast Growth Factor 2, pubmed-meshheading:9843151-Mice, pubmed-meshheading:9843151-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:9843151-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:9843151-Mitogen-Activated Protein Kinases, pubmed-meshheading:9843151-Molecular Structure, pubmed-meshheading:9843151-Nerve Tissue Proteins, pubmed-meshheading:9843151-Neurites, pubmed-meshheading:9843151-Neuroprotective Agents, pubmed-meshheading:9843151-Protein Kinase C, pubmed-meshheading:9843151-Pyrimidines, pubmed-meshheading:9843151-Signal Transduction
pubmed:year
1998
pubmed:articleTitle
A novel neurotrophic pyrimidine compound MS-818 enhances neurotrophic effects of basic fibroblast growth factor.
pubmed:affiliation
Department of Neurology, Tokyo Medical and Dental University, School of Medicine, Japan.
pubmed:publicationType
Journal Article