Document Detail

Matrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role of two AP-1 elements.
MedLine Citation:
PMID:  18072934     Owner:  NLM     Status:  MEDLINE    
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.
Kwang Soo Kim; Hee Young Kim; Eun-Hye Joe; Ilo Jou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  410     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-22     Completed Date:  2008-03-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  605-11     Citation Subset:  IM    
Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea 442-721.
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MeSH Terms
Astrocytes / enzymology*
Base Sequence
Blotting, Western
Brain / cytology,  enzymology*
DNA Primers
Electrophoretic Mobility Shift Assay
Enzyme Induction
Gangliosides / pharmacology
Interferon-gamma / pharmacology
JNK Mitogen-Activated Protein Kinases / metabolism
Lipopolysaccharides / pharmacology
Matrix Metalloproteinase 3 / biosynthesis*,  genetics
Promoter Regions, Genetic
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor AP-1 / physiology*
Transcription, Genetic
Reg. No./Substance:
0/DNA Primers; 0/Gangliosides; 0/Lipopolysaccharides; 0/Transcription Factor AP-1; 82115-62-6/Interferon-gamma; 9007-49-2/DNA; EC Mitogen-Activated Protein Kinases; EC Metalloproteinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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