Activated isoforms of MMP-2 are induced in U87 human glioma cells in response to β-amyloid peptide
✍ Scribed by Suman Deb; J. Wenjun Zhang; Paul E. Gottschall
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 212 KB
- Volume
- 55
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Prior studies using rat primary hippocampal cultures indicated induction of matrix metalloproteinases (MMPs) in response to -amyloid (A). Hence, it was of interest to determine whether MMP activity in a human cell line is influenced by A. A, but not interleukin-1 (IL-1) or lipopolysaccharide (LPS), stimulated an active form of MMP-2 in human U87 glioblastoma cells, as well as increased the expression of the well-known activator of MMP-2, membranetype (MT)-MMP. Activation experiments carried out with amino phenyl mercuric acetate (APMA), immunoprecipitation, as well as immunoblotting, suggest that the lower molecular weight, gelatin-degrading activity was an activated form of MMP-2. Furthermore, it was demonstrated that a synthetic furin convertase inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, decreased the production of Ainduced active MMP-2 in U87 cells. The induction of MMP-3 by cytokines, but not by A, suggests that the effect of A on MMP-2 is selective. Although A stimulated tissue inhibtor of metalloproteinase-1 (TIMP-1), there was no obvious effect of A on TIMP-2 production in U87 cells. These results demonstrate that A induces an active form of MMP-2 likely by increasing the expression of MT-MMP in a human glioblastoma cell line. Active MMP-2 may degrade A or act on ECM components critical in neuronal survival mechanisms and possibly play a role in Alzheimer's disease (AD) neuropathology.