Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serine esterase TL2 from human T4+ lymphocytes is a binding component to HIV-1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism. Recombinant variants of the Kunitz-type serine proteinase inhibitor aprotinin were investigated for their ability to inhibit tryptase TL2 and the binding of gp120 to this enzyme. Furthermore, the viral replication of HIV-1 was investigated H9 cell cultures under the influence of recombinant aprotinin and bikunin variants. In contrast to native aprotinin, the recombinant variant [Arg15, Phe17, Glu52] aprotinin with a reactive-site sequence homologous to the V3 loop of HIV-1 gp120 showed a specific inhibition of tryptase TL2 (> 80%). However, the [Leu15, Phe17, Glu52] aprotinin variant with hydrophobic subsites was the most potent inhibitor of the binding of gp120 to tryptase TL2 (68%). Our results show that the enzyme activity of purified tryptase TL2 is inhibited not only by variants with basic amino acids, but also those with hydrophobic residues in the reactive-site region. Therefore, tryptase TL2 is not a typical trypsin-like or chymotrypsin-like protease. Investigations on inhibition of HIV-1 replication in H9 cell cultures showed that tryptase TL2 is involved in the mechanism of virus internalization into human lymphocytes. The [Leu15, Phe17, Glu52] aprotinin showed a significant retardation of syncytium formation over a period of 5 days in a 1 micro M concentration. Similar investigations were performed with recombinant variants of bikunin, the light chain of human inter-alpha-trypsin inhibitor. Only the single-headed variant [Arg94] delta 2 bikunin inhibited slightly the syncytium formation over a period of 2 days in a 2.2 micro M concentration. Wild-type bikunin and all full-length variants showed no effect, possibly due to steric hindrance by the second domain of the double-headed inhibitor.
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PMID:Inhibition of tryptase TL2 from human T4+ lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. 926 27

Oral treponemes are considered to be important in the development and progression of periodontal diseases. We investigated the mechanisms of recognition and activation of human gingival epithelial cells (HGEC) with the oral treponemes Treponema denticola, Treponema vincentii, and Treponema medium and their outer membrane extracts (OMEs). T. vincentii and T. medium but not T. denticola produced interleukin 8 (IL-8) in an HGEC culture. Further, all three treponemes induced IL-8 mRNA expression and NF-kappaB activation in HGEC. Among them, T. denticola especially exhibited trypsin- and chymotrypsin-like protease activities, and the addition of chymostatin, a chymotrypsin protease inhibitor, resulted in detectable IL-8 production by HGEC cultured with T. denticola. Additionally, IL-8 mRNA expression in HGEC cultured with the three treponemes and their OMEs was definitely inhibited by the mouse anti-human Toll-like receptor 2 (TLR2) monoclonal antibody TL2.1. These findings suggest that oral treponemes and their OMEs activate HGEC through TLR2.
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PMID:Oral treponemes and their outer membrane extracts activate human gingival epithelial cells through toll-like receptor 2. 1254 May 50

TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) was produced mainly as inclusion bodies (IBs) by recombinant Escherichia coli with a temperature-inducible expression system. The yield of TRAIL type 2 IBs at higher preinduction specific growth rate (mu = 0.15 h-1) was higher than that of TRAIL type 1 IBs at lower preinduction specific growth rate (mu = 0.05 h-1). With the same optimized refolding protocols, two types of IBs exhibited different refolding features. Refolded type 1 IBs had higher recovery of more than 80% compared with type 2 IBs (57-63%). By the measurements of fluorescence and CD spectroscopy, type 1 TRAIL IBs dissolved by urea appeared to be a closer secondary structure to the native TRAIL than type 2. Furthermore, with trypsin treatment, the striking decrease in stability of type 1 IBs against protease digestion cannot be attributed to their small size particles observed by scanning electron microscope and probably depend on different protein structure properties between the two IBs. Different properties of inclusion bodies were mainly influenced by different physiological states of the cells just prior to the induction.
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PMID:Refolding and structural characteristic of TRAIL/Apo2L inclusion bodies from different specific growth rates of recombinant Escherichia coli. 1726

Medulloblastoma is a malignant invasive embryonal tumor, occurring in children mainly. It is rare in adults (<1% of adult brain tumors), and so comprehensive cytogenetic and molecular biological data on adult medulloblastomas are very limited. Conventional therapies provide disappointing long-term disease control, and new therapeutic options are being tested. We performed comprehensive cytogenetic analyses of an adult medulloblastoma, WHO grade IV, using trypsin-Giemsa staining (GTG-banding), multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH, complemented by molecular karyotyping using high-density single nucleotide polymorphism (SNP) arrays. GTG-banding of 25 metaphases revealed 31 structural chromosomal aberrations, predominantly located on chromosomes 4q, 9q, 10q, 11p, and 20q, which were confirmed by M-FISH. Two novel, so far not described translocations were found: t(4;11)(q25;p15) and t(9;20)(p23;p12). GTG-banding, locus-specific FISH, and M-FISH detected numerical changes of chromosomes 8, 14, 18, 19, 20, 21, and 22. Molecular karyotyping by SNP array confirmed chromosomal changes -2p, -10q, -16q, and -Xq and revealed de novo partial uniparental disomy 1q and 9q. Applying an upcoming therapeutic approach, we found that primary medulloblastoma cells were resistant to TRAIL, a novel anticancer cytokine, but could be efficiently sensitized by cotreatment with the proteasome inhibitor bortezomib. Bortezomib-TRAIL cotreatment may serve as a powerful therapeutic option for medulloblastoma patients.
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PMID:Cytogenetic and molecular biological characterization of an adult medulloblastoma. 1795 65

Endometriosis is a disease that causes the health of women of reproductive age to deteriorate. The implantation theory is the most widely accepted pathogenesis of the disease, although many points remain poorly understood concerning this theory. According to this theory, regurgitated endometrial debris has to go through various sequential events for the disease to develop. Recent studies have elucidated several aspects of these events. A remarkably reduced gene expression of GnRH II and an increase in uterine contraction-induced IL-8 secretion are suggested to be pathogenic changes in the eutopic endometrium of women with endometriosis. An increased level of osteoprotegerin in the peritoneal fluid of women with endometriosis is suggested to impede tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of endometriotic cells. An increase in the concentration of hepatocyte growth factor and a decrease in the concentration of interferon gamma-inducible protein-10 in the peritoneal fluid of women with endometriosis may stimulate the angiogenesis and development of endometriosis. Midkine, the concentration of which is very high in the follicular fluid of the ovary, may stimulate the growth of endometriosis at the time of ovulation. Immune cells, such as macrophages, lymphocytes, mast cells, and neutrophils, in endometriotic lesions are suggested to play important roles in the progression of the disease. For example, IL-4 from Th2 cells, IL-17 from Th17 cells, tryptase from mast cells, and some serine proteases from neutrophils have been shown to stimulate endometriotic stromal cells, suggesting their specific roles in endometriosis. Interestingly, adiponectin, a key factor in metabolism, also appears to be involved in the pathogenesis of endometriosis. These novel findings sustain the current understanding of the pathogenesis of endometriosis.
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PMID:Current concepts of the pathogenesis of endometriosis. 2969 25


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