2024-03-28T16:29:31Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1165142016-02-18T03:16:33Zcom_10261_105com_10261_1col_10261_358
2015-06-12T11:20:25Z
urn:hdl:10261/116514
Activation of Matrix Metalloproteinase-3 and Agrin Cleavage in Cerebral Ischemia/Reperfusion
Solé, Sònia
Petegnief, Valérie
Gorina, Roser
Chamorro, Ángel
Planas, Anna M.
Matrix metalloproteinase
Ischemia/Reperfusion
Agrin
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.
2015-06-12T11:20:25Z
2015-06-12T11:20:25Z
2004
2015-06-12T11:20:26Z
artículo
Journal of Neuropathology and Experimental Neurology 63(4): 338-349 (2004)
http://hdl.handle.net/10261/116514
eng
closedAccess
American Association of Neuropathologists