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Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1alpha stabilization in the host brain
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chu, Kon | - |
dc.contributor.author | Jung, Keun-Hwa | - |
dc.contributor.author | Kim, Se-Jeong | - |
dc.contributor.author | Lee, Soon-Tae | - |
dc.contributor.author | Kim, Juhyun | - |
dc.contributor.author | Park, Hee-Kwon | - |
dc.contributor.author | Song, Eun-Cheol | - |
dc.contributor.author | Kim, Seung U | - |
dc.contributor.author | Kim, Manho | - |
dc.contributor.author | Lee, Sang Kun | - |
dc.contributor.author | Roh, Jae-Kyu | - |
dc.date.accessioned | 2010-06-25T07:18:36Z | - |
dc.date.available | 2010-06-25T07:18:36Z | - |
dc.date.issued | 2008-03-29 | - |
dc.identifier.citation | Brain Res. 1207, 182-192 | en |
dc.identifier.issn | 0006-8993 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18371939 | - |
dc.identifier.uri | http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6SYR-4S01WNN-4-N&_cdi=4841&_user=168665&_orig=search&_coverDate=05%2F01%2F2008&_sk=987929999&view=c&wchp=dGLbVzz-zSkWz&md5=0cd6644708b4640eb9a9b536aa3179cb&ie=/sdarticle.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/67831 | - |
dc.description.abstract | Hypoxia-inducible factor-1 (HIF-1) plays important roles in the prevention of cerebral ischemia. Deferoxamine (DFX), an iron chelator stabilizes the HIF-1alpha and activates target genes involved in compensation for ischemia. In this study, we are to investigate whether HIF-1alpha can be stabilized in human neural stem cells (NSCs) by DFX, and pre-transplantation of NSCs with HIF-1alpha stabilization can induce prolonged ischemic tolerance. In the DFX-treated NSCs, the HIF-1alpha protein expression was increased about 100-fold time-dependently, and subsequent transcriptional activation (VEGF, BDNF and CXCR4) was also observed. To test an ability to induce ischemic prevention in vivo, DFX-treated NSCs or naive NSCs were transplanted in the striatum of adult rats. Seven days following the transplantation, focal cerebral ischemia was done. Infarct volumes were reduced in both NSCs-transplanted groups, compared with ischemia-only, but more reduced in DFX-treated NSCs group. The protective effects of NSCs were ablated when HIF-1alpha was silenced. HIF-1alpha protein levels were increased in both NSCs-transplanted groups, but more increased in DFX-treated NSCs group. RT-PCR analysis manifested a downregulation of mRNA expression of TNF-alpha, IL-6 and MMP-9 in both NSCs groups, but further decrease in DFX-treated NSCs group. These findings provide evidence that HIF-1alpha stabilization in human NSCs can be achieved effectively by DFX, and HIF-1alpha-stabilized NSCs protect against ischemia in a preventive mode. | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Animals | en |
dc.subject | Brain/metabolism/surgery | en |
dc.subject | Brain Infarction/prevention & control | en |
dc.subject | Brain Ischemia/pathology/prevention & control/*surgery | en |
dc.subject | Chemokine CXCL12/pharmacology | en |
dc.subject | Cyclooxygenase 2/metabolism | en |
dc.subject | Deferoxamine/pharmacology | en |
dc.subject | Disease Models, Animal | en |
dc.subject | Dose-Response Relationship, Drug | en |
dc.subject | Flow Cytometry/methods | en |
dc.subject | Gene Expression Regulation/drug effects | en |
dc.subject | Humans | en |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit/drug effects/*metabolism | en |
dc.subject | Neurons/drug effects/*physiology | en |
dc.subject | Rats | en |
dc.subject | Receptors, CXCR4/metabolism | en |
dc.subject | Siderophores/pharmacology | en |
dc.subject | Stem Cell Transplantation/*methods | en |
dc.subject | Stem Cells/drug effects/*physiology | en |
dc.subject | Time Factors | en |
dc.subject | Up-Regulation/physiology | en |
dc.subject | Vascular Endothelial Growth Factor A/metabolism | en |
dc.title | Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1alpha stabilization in the host brain | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 주건 | - |
dc.contributor.AlternativeAuthor | 정근화 | - |
dc.contributor.AlternativeAuthor | 김세정 | - |
dc.contributor.AlternativeAuthor | 이순태 | - |
dc.contributor.AlternativeAuthor | 김주현 | - |
dc.contributor.AlternativeAuthor | 박희권 | - |
dc.contributor.AlternativeAuthor | 송은철 | - |
dc.contributor.AlternativeAuthor | 김승유 | - |
dc.contributor.AlternativeAuthor | 김만호 | - |
dc.contributor.AlternativeAuthor | 이상건 | - |
dc.contributor.AlternativeAuthor | 노재규 | - |
dc.identifier.doi | 10.1016/j.brainres.2008.02.043 | - |
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