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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
dc.contributor.authorKim, KS-
dc.contributor.authorKim, HY-
dc.contributor.authorJoe, EH-
dc.contributor.authorJou, I-
dc.date.accessioned2010-12-17T02:56:23Z-
dc.date.available2010-12-17T02:56:23Z-
dc.date.issued2008-
dc.identifier.issn0264-6021-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/651-
dc.description.abstractMany 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.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAstrocytes/enzymology*-
dc.subject.MESHBase Sequence-
dc.subject.MESHBlotting, Western-
dc.subject.MESHBrain/cytology-
dc.subject.MESHBrain/enzymology*-
dc.subject.MESHDNA-
dc.subject.MESHDNA Primers-
dc.subject.MESHElectrophoretic Mobility Shift Assay-
dc.subject.MESHEnzyme Induction-
dc.subject.MESHGangliosides/pharmacology-
dc.subject.MESHInterferon-gamma/pharmacology-
dc.subject.MESHJNK Mitogen-Activated Protein Kinases/metabolism-
dc.subject.MESHLipopolysaccharides/pharmacology-
dc.subject.MESHMatrix Metalloproteinase 3/biosynthesis*-
dc.subject.MESHMatrix Metalloproteinase 3/genetics-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHTranscription Factor AP-1/physiology*-
dc.subject.MESHTranscription, Genetic-
dc.titleMatrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role of two AP-1 elements.-
dc.typeArticle-
dc.identifier.pmid18072934-
dc.identifier.urlhttp://www.biochemj.org/bj/410/0605/bj4100605.htm-
dc.contributor.affiliatedAuthor조, 은혜-
dc.contributor.affiliatedAuthor주, 일로-
dc.type.localJournal Papers-
dc.identifier.doi10.1042/BJ20071207-
dc.citation.titleThe Biochemical journal-
dc.citation.volume410-
dc.citation.number3-
dc.citation.date2008-
dc.citation.startPage605-
dc.citation.endPage611-
dc.identifier.bibliographicCitationThe Biochemical journal, 410(3):605-611, 2008-
dc.identifier.eissn1470-8728-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology

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