RGD Reference Report - U0126 prevents ERK pathway phosphorylation and interleukin-1beta mRNA production after cerebral ischemia. - Rat Genome Database

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U0126 prevents ERK pathway phosphorylation and interleukin-1beta mRNA production after cerebral ischemia.

Authors: Wang, ZQ  Chen, XC  Yang, GY  Zhou, LF 
Citation: Wang ZQ, etal., Chin Med Sci J. 2004 Dec;19(4):270-5.
RGD ID: 1582281
Pubmed: PMID:15669185   (View Abstract at PubMed)

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.




  
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Original Reference(s)
MAPK1Humanbrain ischemia  ISOMapk1 (Mus musculus) RGD 
Mapk1Ratbrain ischemia  ISOMapk1 (Mus musculus) RGD 
Mapk1Mousebrain ischemia  IEP  RGD 


Genes (Rattus norvegicus)
Mapk1  (mitogen activated protein kinase 1)

Genes (Mus musculus)
Mapk1  (mitogen-activated protein kinase 1)

Genes (Homo sapiens)
MAPK1  (mitogen-activated protein kinase 1)