title: Apoptosis signal-regulating kinase 1 (Ask1) targeted small interfering RNA on ischemic neuronal cell death.
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.
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Kyoung-Joo
authors.initials: KJ
authors.lastname: Cho
authors.forename: Su Kyoung
authors.initials: SK
authors.lastname: Lee
authors.forename: Gyung W
authors.initials: GW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D034741:RNA, Small Interfering; D015424:Reperfusion; D020521:Stroke / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D034741:RNA, Small Interfering; D048848:MAP Kinase Kinase Kinase 5