Matrix metalloproteinases and their inhibitors in hypoxia/reoxygenation and stroke

2001 ◽  
pp. 275-285 ◽  
Author(s):  
Ariel Miller ◽  
Yaara Ben-Yosef ◽  
Clara Braker ◽  
Sarah Shapiro
2004 ◽  
Vol 24 (7) ◽  
pp. 720-727 ◽  
Author(s):  
Sun-Ryung Lee ◽  
Eng H. Lo

Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral ischemia by degrading matrix components in the neurovascular unit. In this study, the authors document a pathway by which MMPs interfere with cell—matrix interactions and trigger caspase-mediated cytotoxicity in brain endothelial cells. Hypoxia—reoxygenation induced endothelial cytotoxicity. Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase mediated. The temporal profile of caspase-3 activation was matched by elevations in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation and reduced endothelial cell death. Degradation of matrix fibronectin confirmed the presence of extracellular proteolysis. Increasing integrin-linked kinase signaling with the β1 integrin-activating antibody (8A2) ameliorated endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to caspase-mediated brain endothelial cell death after hypoxia—reoxygenation by disrupting cell—matrix interactions and homeostatic integrin signaling.


2003 ◽  
Vol 70 ◽  
pp. 125-133 ◽  
Author(s):  
Tim E. Cawston ◽  
Jenny M. Milner ◽  
Jon B. Catterall ◽  
Andrew D. Rowan

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.


1998 ◽  
Vol 5 (1) ◽  
pp. 187A-187A
Author(s):  
J CARVAJAL ◽  
S KATO ◽  
J SAEZ ◽  
F LEIGHTON ◽  
G VALENZUELA ◽  
...  

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