RGD Reference Report - Cardiac ischemia-reperfusion injury induces matrix metalloproteinase-2 expression through the AP-1 components FosB and JunB. - Rat Genome Database

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Cardiac ischemia-reperfusion injury induces matrix metalloproteinase-2 expression through the AP-1 components FosB and JunB.

Authors: Alfonso-Jaume, MA  Bergman, MR  Mahimkar, R  Cheng, S  Jin, ZQ  Karliner, JS  Lovett, DH 
Citation: Alfonso-Jaume MA, etal., Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1838-46. Epub 2006 May 12.
RGD ID: 1582614
Pubmed: PMID:16699069   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00026.2006   (Journal Full-text)

Matrix metalloproteinase-2 (MMP-2) is a central component of the response to injury in the heart. During ischemia, MMP-2 influences ventricular performance and is a determinant of postinfarction remodeling. Elevation of MMP-2 during reperfusion after ischemia suggests that new protein is synthesized, but the molecular regulation of MMP-2 generation during ischemia-reperfusion (I/R) injury has not been studied. Using the MMP-2 promoter linked to a beta-galactosidase reporter in transgenic mice, we investigated the transcriptional regulation and cellular sources of MMP-2 in isolated, perfused mouse hearts subjected to acute global I/R injury. I/R injury induced a rapid activation of MMP-2 promoter activity with the appearance of beta-galactosidase antigen in cardiomyocytes, fibroblasts, and endothelial cells. Activation of intrinsic MMP-2 transcription and translation was confirmed by real-time PCR and quantitative Western blot analyses. MMP-2 transcription and translation were inhibited by perfusion with 1.0 mM hydroxyl radical scavenger N-(-2-mercaptopropionyl)-glycine. Nuclear extracts demonstrated increased abundance of two activator proteins-1 (AP-1) components JunB and FosB following I/R injury. Immunohistochemical staining localized JunB and FosB proteins to the nuclei of all three cardiac cell types following I/R injury, consistent with enhanced nuclear transport of these transcription factors. Chromatin immunoprecipitation (ChIP) of the AP-1 binding site in the intrinsic murine MMP-2 promoter yielded only JunB under control conditions, whereas ChIP following I/R injury recovered both JunB and FosB, consistent with a change in occupancy from JunB homodimers in controls to JunB/FosB heterodimers following I/R injury. We conclude that enhanced MMP-2 transcription and translation following I/R injury are mediated by induction, via oxidant stress, of discrete AP-1 transcription factor components.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP2HumanMyocardial Reperfusion Injury  ISOMmp2 (Mus musculus) RGD 
Mmp2RatMyocardial Reperfusion Injury  ISOMmp2 (Mus musculus) RGD 
Mmp2MouseMyocardial Reperfusion Injury  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp2  (matrix metallopeptidase 2)

Genes (Mus musculus)
Mmp2  (matrix metallopeptidase 2)

Genes (Homo sapiens)
MMP2  (matrix metallopeptidase 2)


Additional Information