|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0001613,
umls-concept:C0003211,
umls-concept:C0007776,
umls-concept:C0022655,
umls-concept:C0027882,
umls-concept:C0031672,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0205314,
umls-concept:C0679622,
umls-concept:C0683626,
umls-concept:C0915106,
umls-concept:C1327616
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2005-7-5
|
|
pubmed:abstractText |
The elevated level of group IIA secretory phospholipase A(2) (sPLA(2)-IIA) activity contributes to neurodegeneration in the cerebral cortex after ischemia. The up-regulation of cyclooxygenase-2 (COX-2) is also relevant to cerebral ischemia in humans. Studies of ischemia with COX-2 inhibitors suggest a clinical benefit. In the present study, we investigated effects of S-2474 on sPLA(2)-IIA-induced cell death in primary cultures of rat cortical neurons, which was established as an in vitro model of brain ischemia. S-2474 is a novel nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 and contains the di-tert-butylphenol antioxidant moiety. S-2474 significantly prevented neurons from undergoing sPLA(2)-IIA-induced cell death. S-2474 completely ameliorated sPLA(2)-IIA-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. sPLA(2) also generated neurotoxic prostaglandin D(2) (PGD(2)) and free radicals from neurons before cell death. S-2474 significantly inhibited the sPLA(2)-IIA-induced generation of PGD(2). The present cortical cultures contained few non-neuronal cells, indicating that S-2474 affected neuronal survival directly, but not indirectly via non-neuronal cells. The inhibitory effect of S-2474 on COX-2 might contribute to its neuroprotective effect. In conclusion, S-2474 exhibits neuroprotective effects against sPLA(2)-IIA. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for stroke via ameliorating neurodegeneration.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Carbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic S-Oxides,
http://linkedlifedata.com/resource/pubmed/chemical/Group II Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Indolizines,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/S 2474,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/indoxam,
http://linkedlifedata.com/resource/pubmed/chemical/thiazolyl blue
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0028-3908
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
49
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
174-84
|
|
pubmed:dateRevised |
2007-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:15996566-Animals,
pubmed-meshheading:15996566-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:15996566-Apoptosis,
pubmed-meshheading:15996566-Carbamates,
pubmed-meshheading:15996566-Cell Count,
pubmed-meshheading:15996566-Cell Size,
pubmed-meshheading:15996566-Cells, Cultured,
pubmed-meshheading:15996566-Cerebral Cortex,
pubmed-meshheading:15996566-Chromatin,
pubmed-meshheading:15996566-Cyclic S-Oxides,
pubmed-meshheading:15996566-Dose-Response Relationship, Drug,
pubmed-meshheading:15996566-Drug Interactions,
pubmed-meshheading:15996566-Embryo, Mammalian,
pubmed-meshheading:15996566-Group II Phospholipases A2,
pubmed-meshheading:15996566-Humans,
pubmed-meshheading:15996566-In Situ Nick-End Labeling,
pubmed-meshheading:15996566-Indolizines,
pubmed-meshheading:15996566-Neurons,
pubmed-meshheading:15996566-Phospholipases A,
pubmed-meshheading:15996566-Rats,
pubmed-meshheading:15996566-Rats, Sprague-Dawley,
pubmed-meshheading:15996566-Tetrazolium Salts,
pubmed-meshheading:15996566-Thiazoles
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase A(2)-induced apoptosis.
|
|
pubmed:affiliation |
Discovery Research Laboratories, Shionogi and Co., Ltd., 12-4, Sagisu 5-Choume, Fukushima-ku, Osaka 553-0002, Japan. yagami@pharmac.med.yokohama-cu.ac.jp
|
|
pubmed:publicationType |
Journal Article,
Comparative Study
|
