Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinase-9 (MMP-9) is a basal-lamina-degrading protease that we have recently shown to be localized in regenerating sciatic nerve. We now demonstrate that MMP-9 colocalizes with growth-associated protein GAP-43 in regenerating nerves in vivo and is involved in vitro in axonal sprouting. By using a PC12 cell model for neuronal sprouting, we analyzed the effects of recombinant MMP-9, MMP-9-neutralizing antibody, and a broad-spectrum MMP inhibitor (Ro 31-9790) on sprout formation, elongation, and branching. Quantitative phase-contrast microscopy showed that MMP-9 elongated neuronal sprouts by 67% and increased their branching by 14% but did not change the number of sprouts relative to nerve growth factor (NGF) treatment. Double immunofluorescence for GAP-43, a marker for growth cones, and alpha-tubulin, a marker for axonal microtubules, showed that MMP-9-treated cells had increased distribution of alpha-tubulin but no effect on GAP-43. Western blot analyses of cell lysates demonstrated that the NGF-induced increase in GAP-43 was unchanged with MMP-9 treatment or inhibition, confirming that MMP-9 had no effect on new sprout formation. However, Ro 31-9790 reduced GAP-43 levels to those seen in untreated cells, suggesting that an MMP other than MMP-9 is important for sprout formation. Finally, phosphorylated neurofilament M (NFM-p), a marker for regenerative elongation, was induced with MMP-9 treatment and was inhibited by the anti-MMP-9 antibody treatment, confirming the role of MMP-9 in axonal elongation. NFM-p colocalized with MMP-9 in regenerating sciatic nerve fibers. These findings suggest that MMP-9 regulates neurite extension in regenerating peripheral nerve fibers and, therefore, might be of therapeutic value in promoting regeneration in vivo.
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PMID:Matrix metalloproteinase-9 promotes nerve growth factor-induced neurite elongation but not new sprout formation in vitro. 1521 89

The role of matrix metalloproteinases (MMP-3 and MMP-9), tissue inhibitor of MMP (TIMP-2), and GAP-43 (growth-associated-protein) in neocerebellar vermis lobules during postnatal histogenesis was studied after challenge with cisplatin (cisPt). CisPt is one of the most effective and widely used cytotoxic agents in the treatment of a variety of malignancies, in both children and adult patients. A single injection of cisPt to 10-day-old rats altered the spatiotemporal MMP/TIMP expression balance and provoked a decrease in GAP43 immunoreactivity. The imbalance appeared one day (PD11) after cisPt injection, producing disorder of cerebellum histogenesis processes in which MMPs might be involved, i.e. genesis of granule cells, Purkinje cell differentiation and synaptogenesis. Following the early injury, a simultaneous increase in MMP and TIMP expression in the ML was noticed at PD17, likely initiating recovery of Purkinje cell dendrite growth and remodelling processes. However, disturbances at the beginning of recovery phase had emerged, probably due to the down-regulation of GAP-43 after cisPt treatment. The data provide further support for the usefulness of cisPt as a tool for the study of morphological and functional changes in the CNS during postnatal development.
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PMID:Cisplatin induces changes in the matrix metalloproteinases and their inhibitors in the developing rat cerebellum. 2300 Jan 97