Apoptosis signal-regulating kinase 1 (Ask1) targeted small interfering RNA on ischemic neuronal cell death.
Brain Res
; 1412: 73-8, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21803338
ABSTRACT
Apoptosis signal-regulating kinase 1 (Ask1) is one of mitogen-activated protein kinase kinase kinase (MAPKKK) for cell differentiation and apoptosis. The aim of the present study is to evaluate whether RNA interference against Ask1 (Ask1-siRNA) down-regulates the expression of Ask1 and prevents apoptotic neuronal cell death after ischemia/reperfusion (I/R) in mice. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1h, followed by reperfusion. The Ask1-siRNA or a control-siRNA was introduced using osmotic pump intracerebroventricularly at 3days before I/R. The expression and mRNA of Ask1 were evaluated by Western blot and RT-PCR after I/R with time. Immunohistochemistry and TUNEL assay were also investigated to evaluate the effect of Ask1 on cerebral infarction by Ask1-siRNA treatment. The expression of Ask1 was increased significantly at 8h after I/R. The level of mRNA and protein of Ask1 down-regulated after treatment of Ask1-siRNA and subsequently cerebral infarction volume was reduced. Our results suggest the increased Ask1 expression induce apoptotic cell death after I/R. And we also demonstrated that Ask1-siRNA attenuates upregulation of Ask1, which was followed by the reduction of infarction in ischemic brain after I/R. Ask1-siRNA could represent a molecular target for prevention of ischemic stroke.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Isquemia Encefálica
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Acidente Vascular Cerebral
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MAP Quinase Quinase Quinase 5
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article