Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chance of life-threatening complications occurring late after brain irradiation limits the efficacy of this form of cancer therapy. The molecular and cellular events that trigger radiation-induced brain damage are still unknown, but since they have the potential to serve as valuable targets for therapeutic intervention they are worth delineating. In this murine study, the effect of irradiation on the expression of molecules which are known to contribute to brain damage in other model systems was examined. Expression of genes encoding cytokines (TNF-alpha/beta, IL-1 alpha/beta, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN-gamma), cytokine receptors (TNF-Rp55 and p75, IL-1R- p60 and p80, IFN-gamma R, and IL-6R), the cell adhesion molecule (ICAM-1), inducible nitric oxide synthetase (iNOS), anti-chymotrypsin (EB22/5.3), and the gliotic marker (GFAP) was evaluated over a 6-month period using a sensitive RNase protection assay (RPA). We had previously demonstrated that within 24 h of brain irradiation there is an acute transitory molecular response involving TNF-alpha, IL-1, ICAM-1, EB22/5.3 and GFAP. This study shows re-elevation of TNF-alpha, EB22/5.3 and GFAP mRNA levels at 2-3 months, but only TNF-alpha mRNA was overexpressed at 6 months. These time points are when neurological abnormalities are seen after higher doses. The data suggest that TNF-alpha may be involved in late brain responses to irradiation and could contribute to clinical symptoms.
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PMID:Delayed molecular responses to brain irradiation. 924 93

Prostate-specific antigen (PSA) is a serine protease secreted by both normal prostate glandular cells and prostate cancer cells. The major proteolytic substrates for PSA are the gel-forming proteins in semen, semenogelin (Sg) I and II. On the basis of the PSA cleavage map for Sg I and II, a series of small peptides (i.e., < or = 7 amino acids) was synthesized and coupled at the COOH terminus to 7-amino-4-methyl coumarin. Using these fluorescently tagged substrates, K(m)s and k(cat)s were determined for PSA hydrolysis, and the substrates were also tested for activity against a panel of purified proteases. Previously, a variety of chymotrypsin substrates have been used to assay the enzymatic activity of PSA. The present studies have identified a peptide sequence with a high degree of specificity for PSA (ie., no detectable hydrolysis by chymotrypsin) and improved K(m)s and k(cat)s over previously used substrates. On the basis of these parameters, the best peptide substrate for PSA has the amino acid sequence HSSKLQ. Using PC-82 human prostate cancer xenografts and human prostate tissues, this PSA substrate was used to document that prostate cancer cells secrete enzymatically active PSA into the extracellular fluid but that once in the blood, PSA is not enzymatically active. On the basis of this information, it should be possible to use the HSSKLQ peptide as a carrier to target peptide-coupled prodrugs for selective activation within sites of PSA-secreting, metastatic prostate cancer cells and not within the blood or other nonprostatic normal tissues.
Cancer Res 1997 Nov 01
PMID:Specific and efficient peptide substrates for assaying the proteolytic activity of prostate-specific antigen. 935 59

The major proteinase inhibitor in horse gram (Dolichos biflorus) is a low molecular weight (approximately 8500) Bowman-Birk inhibitor (BBI), HGI-III, that inhibits both trypsin and chymotrypsin simultaneously. Analysis of the reactivity of the polyclonal antibodies raised against native HGI-III, with tryptic, lysylendoproteinase-C and CNBr peptides, in dot-blot assays, revealed the presence of three sequential epitopes (Asp1-Lys14 (I), Leu37-Lys63 (II) and Asp64-Lys71 (III)). Of these, epitope II and III occur consecutively in the sequence of HGI-III. The reactive site peptide bonds were identified by cleavage with catalytic quantities of either trypsin or chymotrypsin at acidic pH. The reactive site peptide bond for trypsin was found to be Lys24-Ser25, whereas for chymotrypsin it was Phe51-Ser52. The highly conserved reactive site loop residues of the Bowman-Birk inhibitors are also conserved in HGI-III. The less immunogenic peptide sequence, Leu37-Lys63, also contains the chymotrypsin reactive site. The recognition of this polypeptide by the immune system provides for a new strategy in the design of ideal, smaller proteinase inhibitors as cancer preventive agents.
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PMID:Antigenic determinants and reactive sites of a trypsin/chymotrypsin double-headed inhibitor from horse gram (Dolichos biflorus). 943 14

Long-term rectal administration of enzyme mixture containing papain, trypsin and chymotrypsin in the same ratio as the preparation Wobe-Mugos E (Mucos Pharma, Germany) was evaluated for their antitumor effects in C57Bl6 inbred mice inoculated with Bl6 melanoma cells. 30% of animals in the test group (3 pcs) have been cured of cancer. In the rest of animals (70%) the survival time was prolonged by 58.3% compared to the control group (from average survival time of 24 days in control group to 38 days in the test group). Based on histological and immunohistochemical evaluation a faster process of metastasizing was found in control group than in the group treated with the polyenzyme preparation. In the case of melanoma Bl6 an antimetastatic effect of the preparation was thus proved.
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PMID:Polyenzyme preparation Wobe-Mugos inhibits growth of solid tumors and development of experimental metastases in mice. 948 6

The Bowman-Birk protease inhibitor (BBI), a serine-protease inhibitor, has been reported to exert both anticarcinogenic and radioprotective activity. In this work we examined whether this effect is mediated through inhibition of serine-proteases of the trypsin-chymotrypsin type. Using linearized forms of BBI, evidence will be provided that the secondary structure, obligatory for the protease inhibitory function, is not necessary for the radioprotective effect. Detailed analysis indicated that the radioprotective effect is correlated with the chymotrypsin-inhibitory region of the molecule. Using a synthetic nonapeptide lacking protease inhibitor activity, the radioprotective effect of the total BBI molecule could be mimicked, indicating that the radioprotective effect is independent of the protease inhibitor function.
Cancer Lett 1998 Mar 13
PMID:The radioprotective potential of the Bowman-Birk protease inhibitor is independent of its secondary structure. 956 99

Cancer patients with weight loss showed urinary excretion of a lipid-mobilizing factor (LMF), determined by the ability to stimulate lipolysis in isolated murine epididymal adipocytes. Such bioactivity was not detectable in the urine of cancer patients without weight loss or in normal subjects. The LMF was purified using a combination of ion exchange, exclusion, and hydrophobic interaction chromatographies to give a single component of apparent Mr 43,000, which showed homology in amino acid sequence with human plasma Zn-alpha2-glycoprotein. Both substances showed the same mobility on denaturing and nondenaturing gels and the same chymotrypsin digestion pattern, both stained heavily for carbohydrate, and they showed similar immunoreactivity. Polyclonal antisera to human plasma Zn-alpha2-glycoprotein was also capable of neutralization of the bioactivity of human LMF in vitro. Using competitive PCR to quantify expression of Zn-alpha2-glycoprotein, we found that only those tumors that were capable of producing a decrease in carcass lipid expressed mRNA for Zn-alpha2-glycoprotein. These results provide strong evidence to suggest that tumor production of Zn-alpha2-glycoprotein is responsible for the lipid catabolism seen in cancer patients.
Cancer Res 1998 Jun 01
PMID:Purification and characterization of a tumor lipid-mobilizing factor. 962 74

Certain protease inhibitors, called the anticarcinogenic protease inhibitors in this review, are capable of preventing carcinogenesis in a wide variety of in vivo and in vitro model systems. The anticarcinogenic protease inhibitors are extremely potent agents with the ability to prevent cancer, with some unique characteristics as anticarcinogenic agents. The anticarcinogenic protease inhibitors have the ability to irreversibly suppress the carcinogenic process. They do not have to be continuously present to suppress carcinogenesis. They can be effective when applied in both in vivo and in vitro carcinogenesis assay systems at long time periods after carcinogen exposure, and are effective as anticarcinogenic agents at extremely low molar concentrations. While several different types of protease inhibitors can prevent the carcinogenic process, the most potent of the anticarcinogenic protease inhibitors on a molar basis are those with the ability to inhibit chymotrypsin or chymotrypsin-like proteases. The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is a potent chymotrypsin inhibitor that has been extensively studied for its ability to prevent carcinogenesis in many different model systems. Much of this review is focused on the characteristics of BBI as the anticarcinogenic protease inhibitor, as this is the protease inhibitor that has risen to the human trial stage as a human cancer chemopreventive agent. Part of this review hypothesizes that the Bowman-Birk family of protease inhibitors plays a role in plants similar to that of alpha1-antichymotrypsin in people. Both BBI and alpha1-antichymotrypsin are potent inhibitors of chymotrypsin and chymotrypsin-like enzymes, are highly anti-inflammatory, and are thought to play important roles in the defense of their respective organisms. It is believed that BBI will be shown to play a major role in the prevention and/or treatment of several different diseases, in addition to cancer.
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PMID:Chemopreventive agents: protease inhibitors. 969 Aug 17

Metastasis is a characteristic and fatal feature of human malignancies. Its regulation is therefore of the utmost significance to clinicians. The present study was undertaken to determine whether a legume-derived protease inhibitor (PI) of trypsin/chymotrypsin, the field bean PI (FBPI), also has plasmin inhibitory activity and can inhibit pulmonary metastasis of B16F10 melanoma cells systemically injected into BDF1 mice. Two approaches to the problem were made. In the first, the melanoma cells were exposed to two different concentrations of the FBPI prior to their inoculation into animals. In the second, the mice were treated intraperitoneally with FBPI at a dose of 100 mg/kg body weight once daily for 10 days, the treatment being started soon after the systemic injection of the tumour cells. The study revealed that both modes of FBPI treatment could effectively block lung cell metastasis by the melanoma cells and that FBPI has plasmin blocking activity. Since urokinase type plasminogen activator and plasmin are known to play significant roles in tumour cell metastasis, the dose-dependent inhibitory effect of FBPI with antiplasmin activity on tumour cell metastasis suggests that its antimetastatogenic action is probably mediated through its plasmin inhibitory action.
Cancer Lett 1998 Jul 03
PMID:The field bean protease inhibitor has the potential to suppress B16F10 melanoma cell lung metastasis in mice. 971 30

SCC antigen is a tumor-associated protein of squamous cell carcinoma of various organs. So far, two genes (SCC Ag-1 and SCC Ag-2) have been identified, and their products are highly homologous and classified as serine protease inhibitors (serpin). Recombinant SCC antigen-1 inhibits chymotrypsin and cathepsin L in vitro, indicating that it is inhibitory type serpin. Transduction of tumor cells with SCC antigen-1 reveals that SCC antigen-1 inhibits apoptosis of tumor cells induced by anticancer drug, TNFalpha or NK cells. Therefore SCC antigen-1 may work in cancer cells for tumor growth, and in normal squamous epithelium for differentiation by means of the inhibition of apoptosis. Recombinant SCC antigen-2 inhibits cathepsin G and mast cell chymase, suggesting that it protects epithelial cells from the inflammation induced by these proteases.
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PMID:Biological role of SCC antigen. 981 78

Certain protease inhibitors are effective at preventing or suppressing carcinogen-induced transformation in vitro and carcinogenesis in animal model systems. One protease inhibitor, the soybean-derived Bowman-Birk inhibitor (BBI) is particularly effective in suppressing carcinogenesis. BBI is a protein of a molecular weight of 8000 with a well-characterized ability to inhibit trypsin and chymotrypsin. BBI has been extensively studied, both as purified BBI and as an extract of soybeans enriched in BBI called BBI concentrate (BBIC). Purified BBI and BBIC have comparable suppressive effects on the carcinogenic process in a variety of in vivo and in vitro systems. BBI appears to be a universal cancer preventive agent. Purified BBI and BBIC suppress carcinogenesis as follows: in 3 different species (mice, rats, and hamsters); in several organ systems and tissue types [eg, colon, liver, lung, esophagus, cheek pouch (oral epithelium), and cells of hematopoietic origin]; and in cells of epithelial and connective tissue origin when given to animals by several different routes of administration, including the diet, leading to different types of cancer (eg, squamous cell carcinomas, adenocarcinomas, and angiosarcomas), and induced by various chemical and physical carcinogens. About half of an oral dose of BBI is taken up into the bloodstream and distributed throughout the body, with excretion via the urine. Pharmacokinetic studies of BBI have been performed in animals with radioactively labeled BBI, whereas antibodies that react with reduced BBI are being used in pharmacokinetic studies in humans. The calculated serum half-life is 10 h in both rats and hamsters. BBIC achieved Investigational New Drug status from the FDA in April 1992 (IND no. 34671; sponsor, Ann R Kennedy), and studies to evaluate BBIC as an anticarcinogenic agent in human populations began. Both BBI and BBIC prevent and suppress malignant transformation in vitro and carcinogenesis in vivo without toxicity.
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PMID:The Bowman-Birk inhibitor from soybeans as an anticarcinogenic agent. 984 8


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