Expression and activation of matrix metalloproteinase-2 and -9 in rat brain after transient focal cerebral ischemia.
Matrix metalloproteinases (MMPs) degrade the extracellular matrix and carry out key functions during development and after injury. By means of zymography, Western blot and immunohistochemistry, we studied MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in rat brain after focal cerebral ischemia. The control rat brain showed constitutive MMP-2 and, to a lesser extent, MMP-9, which were mainly present as prozymogens. MMP-2 protein was located in the cell body of neurons, glia, and endothelium, whereas MMP-9 was associated to neurons and myelinated fibre tracts. Ischemia greatly increased MMP activation in two temporal waves, in the first one, MMP-9 protein was induced from 4 h to 4 days, and also a small and short-lasting increase in MMP-2 was detected at 4 h. The second wave showed a massive increase in MMP-2 protein expression and activation by day 4, which was compatible with abundant MMP-2 in reactive microglia/macrophages. Our results are compatible with progressive induction of MMP-9 proform, likely in neurons, shortly after ischemia. For MMP-2, the results suggest a discrete production immediately after reperfusion, while a very enhanced expression and activation of MMP-2 attributable to microglia/macrophages occurs on day 4, and it might contribute to the phagocytic action of these reactive cells.
Planas
A M
AM
Departament de Farmacologia i Toxicologia, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain.
Solé
S
S
Justicia
C
C
D000818:Animals; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology; D004789:Enzyme Activation; D004790:Enzyme Induction; D004792:Enzyme Precursors / Q000378:metabolism; D007124:Immunoenzyme Techniques; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology; D013997:Time Factors
D004792:Enzyme Precursors; D009419:Nerve Tissue Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9