rdf:type |
|
lifeskim:mentions |
umls-concept:C0004112,
umls-concept:C0006100,
umls-concept:C0017262,
umls-concept:C0109317,
umls-concept:C0165519,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1622501,
umls-concept:C1704259,
umls-concept:C1705455,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1705987,
umls-concept:C2911684
|
pubmed:issue |
6
|
pubmed:dateCreated |
2008-3-18
|
pubmed:abstractText |
Many reports have shown that matrix metalloproteinase (MMP)-9 plays an important role in brain inflammation and diseases. In our previous study, bradykinin (BK) has been shown to induce proMMP-9 expression via MAPKs and NF-kappaB in rat brain astrocytes (RBA-1). However, the molecular mechanisms and physiological roles underlying BK-induced MMP-9 expression in RBA-1 remain unclear. Here we reported that BK induced proMMP-9 expression and promoted RBA-1 cell migration, via a B(2) BK receptor-activated protein kinase C-delta (PKC-delta)-dependent signaling pathway. Activation of PKC-delta led to phosphorylation and translocation of extracellular signal-regulated kinase 1/2 (ERK1/2) and then activated a transcription factor Elk-1. Phospho-Elk-1 bound to MMP-9 promoter and thereby induced transcription of MMP-9. The rat MMP-9 promoter containing an Elk-1 cis-binding site (Ets domain), that located at nucleotides -511 to -506 was identified as a crucial domain linking to BK action. Moreover, BK induced recruitment of p300 (as a transcriptional co-activator) to the MMP-9 promoter, leading to the acetylation of histone H4 in chromatin and facilitating MMP-9 gene transcription. Taken together, these results suggested that in RBA-1 cells, activation of ERK1/2 by a PKC-delta-dependent event mediated through Elk-1 pathway is essential for MMP-9 gene up-regulation and cell migration induced by BK.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0894-1491
|
pubmed:author |
|
pubmed:copyrightInfo |
(c) 2008 Wiley-Liss, Inc.
|
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
56
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
619-32
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:18240315-Analysis of Variance,
pubmed-meshheading:18240315-Animals,
pubmed-meshheading:18240315-Astrocytes,
pubmed-meshheading:18240315-Bradykinin,
pubmed-meshheading:18240315-Brain,
pubmed-meshheading:18240315-Cell Line, Transformed,
pubmed-meshheading:18240315-Cell Movement,
pubmed-meshheading:18240315-Dose-Response Relationship, Drug,
pubmed-meshheading:18240315-Drug Interactions,
pubmed-meshheading:18240315-Enzyme Inhibitors,
pubmed-meshheading:18240315-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18240315-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:18240315-Matrix Metalloproteinase 9,
pubmed-meshheading:18240315-Protein Kinase C-delta,
pubmed-meshheading:18240315-Rats,
pubmed-meshheading:18240315-Signal Transduction,
pubmed-meshheading:18240315-Time Factors
|
pubmed:year |
2008
|
pubmed:articleTitle |
Bradykinin induces matrix metalloproteinase-9 expression and cell migration through a PKC-delta-dependent ERK/Elk-1 pathway in astrocytes.
|
pubmed:affiliation |
Department of Pharmacology, Chang Gung University, Tao-Yuan, Taiwan.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|