RGD Reference Report - Activation of matrix metalloproteinase-3 and agrin cleavage in cerebral ischemia/reperfusion. - Rat Genome Database

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Activation of matrix metalloproteinase-3 and agrin cleavage in cerebral ischemia/reperfusion.

Authors: Sole, S  Petegnief, V  Gorina, R  Chamorro, A  Planas, AM 
Citation: Sole S, etal., J Neuropathol Exp Neurol. 2004 Apr;63(4):338-49.
RGD ID: 2325962
Pubmed: PMID:15099024   (View Abstract at PubMed)

Matrix metalloproteinase-3 (MMP-3) degrades components of the extracellular matrix and may participate in the pathogenesis of stroke. Here we examine the expression, activation, and cellular location of MMP-3 and the cleavage of agrin, an MMP-3 substrate, following transient middle cerebral artery occlusion in the rat. MMP-3 was activated by ischemia/reperfusion, which was revealed by the appearance of a cleaved form and increased degradation of a substrate. MMP-3 was observed in ischemic neurons, oligodendrocytes, microvasculature, and reactive microglia/macrophages. In cell cultures, MMP-3 expression was observed in neurons and, to a lesser extent, in mature oligodendrocytes, but not in oligodendrocyte progenitors, astrocytes, or microglia. Casein zymography revealed MMP-3 in cultured neurons. Agrin was expressed in cultured neurons and cultured astrocytes. In brain tissue, agrin was detected in neurons, and following ischemia it was also detected in reactive astrocytes. Addition of MMP-3 to protein extracts from control brain caused neuronal agrin degradation. Following ischemia/reperfusion, agrin disappeared from the tissue membrane fraction and a cleaved agrin fragment was found in tissue protein extracts. The present results show MMP-3 activation and neuronal transmembrane agrin cleavage after ischemia/reperfusion. In addition, the finding that MMP-3 cleaves brain agrin strongly suggests that ischemia-induced MMP-3 activation causes agrin cleavage.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP3HumanReperfusion Injury  ISOMmp3 (Rattus norvegicus)protein:increased protein and activity:brainRGD 
Mmp3RatReperfusion Injury  IEP protein:increased protein and activity:brainRGD 
Mmp3MouseReperfusion Injury  ISOMmp3 (Rattus norvegicus)protein:increased protein and activity:brainRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mmp3Ratresponse to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp3  (matrix metallopeptidase 3)

Genes (Mus musculus)
Mmp3  (matrix metallopeptidase 3)

Genes (Homo sapiens)
MMP3  (matrix metallopeptidase 3)


Additional Information