Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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