87 482

Cited 16 times in

Matrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role of two AP-1 elements.

Kim, KS; Kim, HY; Joe, EH; Jou, I
The Biochemical journal, 410(3):605-611, 2008
Journal Title
The Biochemical journal
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.
MeSH terms
AnimalsAstrocytes/enzymology*Base SequenceBlotting, WesternBrain/cytologyBrain/enzymology*DNADNA PrimersElectrophoretic Mobility Shift AssayEnzyme InductionGangliosides/pharmacologyInterferon-gamma/pharmacologyJNK Mitogen-Activated Protein Kinases/metabolismLipopolysaccharides/pharmacologyMatrix Metalloproteinase 3/biosynthesis*Matrix Metalloproteinase 3/geneticsPromoter Regions, GeneticRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionTranscription Factor AP-1/physiology*Transcription, Genetic
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
조, 은혜주, 일로
Full Text Link
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.