Hsp 70.1의유전자Knock-Out이국소뇌허혈모델에서사립체Cytochrome C의세포질유리에미치는효과에관한연구

Abstract

Department of Neurology, Seoul National University; Neuroscience Research Institute, SNUMRC and ClinicalResearch Institute, Seoul National University Hospital, Seoul. Background: HSP70 protein in mice, which is produced from two genes, hsp70.1 and hsp70.3, is known to pro-tect the brain against ischemic injury. However, little information is available on the anti-apoptotic mechanism ofHSP70.1 protein after cerebral ischemia. To evaluate the role of HSP70.1 in ischemia, we analyzed cytochrome crelease and nuclear fragmentation using hsp70.1 knock-out (KO) mice and their wild-type (WT) mice. Methods:hsp70.1 KO and WT mice underwent focal ischemia for 120 minutes. Morphological analysis was performed byNissl staining and Hoechst 33342 staining. HSP70 expression and cytochrome c release were analyzed by Westernblotting and immunohistochemistry.Reseults: Following focal ischemia, HSP70 protein expression was markedlysuppressed in KO mice versus WT mice. KO mice showed a significantly greater infarction volume and nuclearfragmentation in the cortex than WT mice at 24 hours after ischemia. At 8 hours, cytochrome c release into thecytosol was markedly higher in KO mice than in WT mice. Conclusions: These findings suggest that the deletionof the hsp70.1 gene increases cytochrome c release into the cytosol, thereby exacerbating apoptosis after focalcerebral ischemia. 대한뇌졸중학회지제6권제1호2004년5월