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Matrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role of two AP-1 elements.
DC Field | Value | Language |
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dc.contributor.author | Kim, KS | - |
dc.contributor.author | Kim, HY | - |
dc.contributor.author | Joe, EH | - |
dc.contributor.author | Jou, I | - |
dc.date.accessioned | 2010-12-17T02:56:23Z | - |
dc.date.available | 2010-12-17T02:56:23Z | - |
dc.date.issued | 2008 | - |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/651 | - |
dc.description.abstract | Many brain cells secrete MMPs (matrix metalloproteinases), and increased or misregulated MMP levels are found in neurodegenerative disorders. Here we report that MMP-3 transcription and protein secretion were increased in rat brain astrocytes stimulated with lipopolysaccharide, gangliosides or interferon-gamma. Sequential deletion of the MMP-3 promoter revealed that sequences between -0.5 kb and the start codon were crucial for the transcriptional induction of MMP-3. In addition, experiments using pharmacological inhibitors of individual mitogen-activated protein kinases revealed that MMP-3 induction and promoter activity involved Jun N-terminal kinase, a representative upstream signal of AP-1 (activator protein-1). Sequence analyses of the region of the MMP-3 promoter 500 bp from the start codon indicated the presence of three AP-1 binding sequences. Among them, electrophoretic-mobility-shift assays as well as site-directed mutagenesis of individual AP-1 sequences revealed that distal and middle, but not proximal, sequences largely mediated its induction. Together, these results indicate that AP-1 could control MMP-3 induction in brain astrocytes and that its regulation through specific AP-1 elements could be exploited in the treatment of brain pathologies in which increased expression of MMP-3 plays crucial roles. | - |
dc.language.iso | en | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Astrocytes | - |
dc.subject.MESH | Base Sequence | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Brain | - |
dc.subject.MESH | DNA | - |
dc.subject.MESH | DNA Primers | - |
dc.subject.MESH | Electrophoretic Mobility Shift Assay | - |
dc.subject.MESH | Enzyme Induction | - |
dc.subject.MESH | Gangliosides | - |
dc.subject.MESH | Interferon-gamma | - |
dc.subject.MESH | JNK Mitogen-Activated Protein Kinases | - |
dc.subject.MESH | Lipopolysaccharides | - |
dc.subject.MESH | Matrix Metalloproteinase 3 | - |
dc.subject.MESH | Promoter Regions, Genetic | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Sprague-Dawley | - |
dc.subject.MESH | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.MESH | Transcription Factor AP-1 | - |
dc.subject.MESH | Transcription, Genetic | - |
dc.title | Matrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role of two AP-1 elements. | - |
dc.type | Article | - |
dc.identifier.pmid | 18072934 | - |
dc.identifier.url | http://www.biochemj.org/bj/410/0605/bj4100605.htm | - |
dc.contributor.affiliatedAuthor | 조, 은혜 | - |
dc.contributor.affiliatedAuthor | 주, 일로 | - |
dc.type.local | Journal Papers | - |
dc.identifier.doi | 10.1042/BJ20071207 | - |
dc.citation.title | The Biochemical journal | - |
dc.citation.volume | 410 | - |
dc.citation.number | 3 | - |
dc.citation.date | 2008 | - |
dc.citation.startPage | 605 | - |
dc.citation.endPage | 611 | - |
dc.identifier.bibliographicCitation | The Biochemical journal, 410(3). : 605-611, 2008 | - |
dc.identifier.eissn | 1470-8728 | - |
dc.relation.journalid | J002646021 | - |
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