Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The earliest observed apoptotic change in a macrophage-like cell line, J774.1, treated with lipopolysaccharide (LPS) in the presence of cycloheximide (CHX) was a selective increase in caspase-3-like activity. The addition of polymyxin B, TPCK, herbimycin A, or genistein, all of which inhibited LPS-induced tumor necrosis factor alpha (TNF-alpha) production by macrophages, suppressed the activation of the caspase-3-like protease in these macrophages treated simultaneously with CHX. However, SB202190 and SB203580, inhibitors of MAP kinase, and PD98059, an inhibitor of MAP-kinase kinase (MEK), showed no effect on the activation of the caspase-3-like protease or on the cell damage of the macrophages treated with LPS and CHX, whereas they inhibited LPS-induced TNF-alpha production. These results suggest that some of the early signals in LPS-treated macrophages are common to the subsequent pathways for TNF-alpha production and caspase-3-like protease activation, but the later signals, like MAP-kinase kinase or MAP-kinase, are not involved in the pathways for caspase-3-like protease activation.
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PMID:LPS-induced signals in activation of caspase-3-like protease, a key enzyme regulating apoptotic cell damage into a macrophage-like cell line, J774.1, in the presence of cycloheximide. 1053 27

The cuticle-degrading proteases from entomopathogensis fungus, Melarhizium anisopliae, were induced by adding cicada exuviae, colloidal chitin, shrimp cuticle, maggot cuticle, horsefly cuticle and silkworm chrysalis cuticle into minimal medium. After ultrafiltration, Ultrogel AcA 54 column and IEF, a protease designated as MAP-21 with Mr 27 kD, and pI 7.6 were purified. It was shown that the recognition site of MAP-21 was Arg, PMSF and TLCK could inhibited the activity of this protease, indicating that there were Ser and His residues in the active center. The inhibitors to trypsin, leupeptin antipain and STI also repressed the activity of MAP-21, while chymostatin, TPCK and elastatinal TEI were shown no inhibition to its activity, demonstrating that, MAP-21 was a trypsin-like protease. Other properties of MAP-21 were also reported.
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PMID:[Purification and characterization of cuticle-degrading protease from entomopathogenic fungus, Metarhizium anisopliae]. 1254 97

Nuclear factor kappa B (NF-kappaB) plays a significant role in immunity and inflammation and represents a first choice as pharmacological target for anti-inflammatory therapy. However, research in this field has been hampered by the fact that no convenient assay suitable for large-scale screening procedures is available. The present study provides a cell death-based assay method for screening of nuclear factor-kappaB inhibitors. In this study, we observed that four distinct pharmacologic inhibitors of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), N-tosyl-L-lysyl chloromethyl ketone (TPCK), genistein and BAY11-7082, resulted in the cell death of murine macrophages, J774A.1. DNA-binding experiments showed that lethal doses were consistent with those required for NF-kappaB inhibition. DNA fragmentation analysis showed that cell death is apoptotic in nature. Further studies suggested that NF-kappaB inhibitors induced apoptosis is independent of the involvement of other markers of cell death such as caspases and p38 MAP (Mitogen activated protein) kinase. From this study, we conclude that NF-kappaB activation may represent an important survival mechanism in macrophages. This study also provides a new cell-based screening method, as any compound that will inhibit NF-kappaB activity will result in the death of macrophages.
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PMID:Development of a cell death-based method for the screening of nuclear factor-kappaB inhibitors. 1843 Apr 34