U0126 prevents ERK pathway phosphorylation and interleukin-1beta mRNA production after cerebral ischemia / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
;
(4): 270-275, 2004.
Article
in English
| WPRIM
| ID: wpr-305485
ABSTRACT
<p><b>OBJECTIVE</b>To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischemic brain.</p><p><b>METHODS</b>Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phosphorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1beta mRNA level was measured by ribonuclease protection assay.</p><p><b>RESULTS</b>Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1beta mRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO.</p><p><b>CONCLUSION</b>Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1beta mRNA via the inhibition of ERK pathway.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Phosphorylation
/
Transcription Factors
/
Butadienes
/
RNA, Messenger
/
Signal Transduction
/
Proto-Oncogene Proteins
/
Interleukin-1
/
Mitogen-Activated Protein Kinase 1
/
Infarction, Middle Cerebral Artery
Limits:
Animals
Language:
English
Journal:
Chinese Medical Sciences Journal
Year:
2004
Type:
Article
Similar
MEDLINE
...
LILACS
LIS