Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of pretreatments of host muscles with metalloproteinases (MMPs) or with notexin on the migration of transplanted myoblasts was investigated. Transgenic TnILacZ mice in which the beta-galactosidase gene is under the control of a quail fast skeletal troponin I gene promoter were used as donors. A polyethylene microtube with four perforations was inserted in the tibialis anterior (TA) of CD1 mice. Both pretreatment substances and cells were slowly injected through that microtube. Muscles were pretreated 2 days before myoblast injection either with a mixture of collagenase, matrilysin, and notexin or with only collagenase and matrilysin or only notexin. As control for our experiments, TnILacZ and C2C12 myoblasts were also injected in TA muscles not pretreated. Comparison of short and long-term myoblast radial migration was performed using a dye (PKH26) and X-gal staining, respectively. The recipient mice were immunosuppressed with FK506. Two days after myoblast transplantation, the cell movement in muscles pretreated with collagenase, matrilysin, and notexin was slightly greater than in muscles pretreated only with collagenase and matrilysin but was about twice that observed in muscles treated with notexin alone. Almost no radial migration of TnILacZ myoblasts was observed in untreated muscles. The C2C12 myoblasts showed a four-to fivefold higher migration capacity than TnILacZ myoblasts. At 15 days after TnILacZ myoblast transplantation, the farthest positive beta-gal muscle fibers show a two- to threefold extension of the initial migration observed at 2 days, demonstrating the ability of myoblasts to continue the migration following all pretreatments and even in the untreated muscles. In addition, more muscle fibers expressed the beta-gal reporter gene in muscles pretreated only with MMPs. Our results clearly demonstrate that muscle pretreatments with MMPs increase myoblast migration and fusion with host muscle fibers after transplantation and that the C2C12 cell line producing MMPs has a higher migratory capacity.
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PMID:Intramuscular migration of myoblasts transplanted after muscle pretreatment with metalloproteinases. 1103 70

Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 have been associated with tumor progression, invasion, and metastasis. The use of synthetic MMP inhibitors to block the proteolytic activity of these enzymes recently emerged as a potential therapeutic tool to treat cancer. In this study, we report that GI129471, a synthetic broad-spectrum MMP inhibitor, efficiently reduced the in vitro invasiveness of HT1080 cells through type IV collagen, a major component of basement membranes. This reduced invasion was paralleled by a complete inhibition of pro-MMP-2 activation; however, GI129471 strongly increased the amount of secreted pro-MMP-9, which could be subsequently activated through a plasminogen-dependent mechanism. Quantitative RT-PCR and northern blot analysis revealed that GI129471 specifically increased the MMP-9 mRNA steady-state level. Moreover, transient transfection of HT1080 cells with beta-galactosidase reporter vectors containing different lengths of the 5'-flanking region of the MMP-9 gene revealed an upregulation of the transcriptional activity of the corresponding promoter. Well-known modulators of MMP-9 expression such as Il-1beta and TNF-alpha were not involved in this upregulation. These findings emphasize the complexity of the regulation of MMP expression and the requirement for a detailed characterization of the potential adverse side effects associated with the use of broad-spectrum MMPIs.
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PMID:Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors. 1192 9

Kaiso is a BTB/POZ transcription factor that functions in vitro as a transcriptional repressor of the matrix metalloproteinase gene matrilysin and the non-canonical Wnt signaling gene Wnt-11, and as an activator of the acetylcholine-receptor-clustering gene rapsyn. Similar to other BTB/POZ proteins (e.g. Bcl-6, PLZF, HIC-1), endogenous Kaiso localizes predominantly to the nuclei of mammalian cells. To date, however, the mechanism of nuclear import for most POZ transcription factors, including Kaiso, remain unknown. Here, we report the identification and characterization of a highly basic nuclear localization signal (NLS) in Kaiso. The functionality of this NLS was verified by its ability to target a heterologous beta-galactosidase/green-fluorescent-protein fusion protein to nuclei. The mutation of one positively charged lysine to alanine in the NLS of full-length Kaiso significantly inhibited its nuclear localization in various cell types. In addition, wild-type Kaiso, but not NLS-defective Kaiso, interacted directly with the nuclear import receptor Importin-alpha2 both in vitro and in vivo. Finally, minimal promoter assays using a sequence-specific Kaiso-binding-site fusion with luciferase as reporter demonstrated that the identified NLS was crucial for Kaiso-mediated transcriptional repression. The identification of a Kaiso NLS thus clarifies the mechanism by which Kaiso translocates to the nucleus to regulate transcription of genes with diverse roles in cell growth and development.
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PMID:Nuclear import of the BTB/POZ transcriptional regulator Kaiso. 1556 77