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

Treatment of the transformed mouse embryo fibroblast cell line AKR-MCA with 1% N,N-dimethylformamide (DMF) resulted in the restoration of a nontransformed phenotype in these cells. In order to determine if an increase in growth inhibitory peptides might be responsible for these changes in growth properties of the DMF-treated AKR-MCA cells we examined the serum-free conditioned medium for its ability to inhibit the anchorage-independent growth of a human colon carcinoma cell line. The extracellular levels of inhibitory activity were two-fold higher in conditioned medium derived from AKR-MCA cells than in AKR-MCA cells grown in 1% DMF (AKR-MCA/DMF). Fractionation of the crude conditioned medium indicated the presence of an Mr 20,000 inhibitory fraction in AKR-MCA/DMF conditioned medium which was reduced in AKR-MCA cells. This Mr 20,000 inhibitory activity was acid and heat stable and sensitive to dithiothreitol and trypsin. In addition to inhibiting the growth of a human colon carcinoma cell line this protein induced colony formation in AKR-2B cells and competed for binding to the transforming growth factor beta (TGF-beta) receptor. Therefore, this Mr 20,000 inhibitory polypeptide induced by DMF is probably TGF-beta. TGF-beta was also shown to inhibit the growth of AKR-MCA cells in monolayer culture.
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PMID:Regulation of growth inhibitory activity in transformed mouse embryo fibroblasts. 288 48

The sonicated supernatant of the sperm of the toad, Bufo japonicus, can digest easily the vitelline coat (VC) of uterine eggs, and to a lesser extent the VC of coelomic eggs, but not that of activated eggs. The VC lysis and fertilization were competitively inhibited in the presence of t-butyloxycarbonyl-L-Gln-L-Arg-L-Arg-4-methylcoumaryl-7-amide (Boc-Gln-Arg-Arg-MCA), suggesting the involvement of proteases in the fertilization process. Starting from a sonicated supernatant, a potent VC lysin, possessing hydrolytic activity on Boc-Gln-Arg-Arg-MCA, was obtained by anion-exchange chromatography and gel filtration. The activity of the partially purified lysin was inhibited by diisopropyl fluorophosphate (DFP) and by such trypsin inhibitors as soybean trypsin inhibitor, leupeptin, and (p-amidinophenyl) methanesulfonyl fluoride hydrochloride, but not by chymostatin, E-64, and ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. The molecular weight of the lysin was estimated to be 32K, based on the fluorographic image of 3H-DFP binding to the lysin on sodium dodecyl sulfate gel electrophoresis. The VC lysin was most active at pH 7.0-7.6 and under low ionic strength equivalent to fresh water. The release of the VC lysin was induced upon incubation of sperm with the contents of oviducal pars recta granules (PRG), which are known to induce the acrosome reaction. We conclude that the protease studied here represents the VC lysin of toad sperm that is involved in fertilization by digesting the VC of uterine eggs, probably released as a result of the acrosome reaction induced by PRG.
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PMID:Classification, inhibition, and specificity studies of the vitelline coat lysin from toad sperm. 323 42

Preclinical alterations of protease activities in skeletal muscles from 10-day-old dystrophic mouse, C57BL/10-mdx, were examined by using 10 fluorogenic peptide substrates. Among the activities tested, only Boc-Val-Pro-Arg-MCA-hydrolyzing enzyme of the muscle microsomes showed an about 6-fold higher level of activity in mdx mouse. The increase in activity was not observed in tissues other than skeletal muscle. The enzyme had a pH optimum between 8.5 and 11.0, and was inhibited with DFP and variety of trypsin inhibitors. The enzymatic activity transiently increased at 1-2 weeks of age, the preclinical or very early stage of the disease. These results imply that the increased level of a trypsin-like protease possibly present in muscle microsomes may be closely related to the manifestation of muscular dystrophy.
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PMID:Preclinical increase in activity of muscle microsomal trypsin-like protease in murine muscular dystrophy, C57BL/10-mdx. 351 21

An inactive form of human urinary kallikrein (inactive HUK) was highly purified from fresh urine collected from healthy men. Inactive HUK was separated from the active kallikrein (HUK) initially presents in the urine by affinity chromatography on a column of aprotinin immobilized on Sepharose 4B and further purified by gel filtration, ion-exchange chromatography and immunoaffinity chromatography on an anti-HUK antibody immobilized Sepharose 4B column. Inactive HUK was rapidly activated by a trace amount of trypsin. While, plasmin, urokinase, thrombin and chymotrypsin caused no activation of inactive HUK. The molecular weights of inactive HUK and HUK were estimated to be 4.8 X 10(4) and 4.5 X 10(4), respectively. The molecular weight of active HUK generated from inactive HUK by the action of trypsin (HUK'') was almost the same as that of HUK. The mobility of inactive HUK was slightly slower than that of HUK on both immunoelectrophoresis and polyacrylamide gel disc electrophoresis. On the other hand, the electrophoretic mobility of HUKK'' was almost the same as that of HUK. These two types of active HUK had no significant difference in the Km values for H-Pro-Phe-Arg-MCA hydrolysis and inhibition profiles by various protease inhibitors and anti-HUK antibody. Inactive HUK was unable to be measured by the direct radioimmunoassay (RIA) but HUK" generated by the action of trypsin could be measured by the RIA.
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PMID:An inactive form of kallikrein in human urine. 354 16

A macromolecule binding 3H-methylcholanthrene (3H-MCA) and 3H-benzo(a)pyrene (3H-BaP) and sedimenting in the 4-5 S region of sucrose gradient (4.5 S) was identified in rat liver cytosol. The binding was displaced by 100-fold molar excess unlabeled ligands whereas 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) was ineffective. The dissociation constant for both polycyclic aromatic hydrocarbons (PAHs) was of the order of 10(-8) M or lower. Both 3H-MCA and 3H-BaP bound to 4.5 S in a non covalent manner, since 92% of the bound radioactivity was extractable with ethyl ether. Furthermore the binding was strongly reduced by urea 8 M and by guanidine. HCl 4 M (99 and 70% respectively). Thin layer chromatography of the ethyl ether-solubilized radioactivity showed a peak comigrating with PAHs used as standards. When chromatographed on Sephadex G-200, 4.5 S was eluted as a sharp peak with an apparent molecular weight of 50-60,000 daltons. Enzyme treatment of liver cytosol showed that the 4.5 S binding sites were destroyed by micrococcal nuclease (92% of inhibition). Papain and phosphodiesterase I and II reduced the binding to 50%, whereas DNase I, DNase II, RNase, phospholipase A2 and C and trypsin were ineffective. These data suggest that the PAHs binding macromolecule of rat liver cytosol is a protein associated with a polynucleotide. The binding of both PAHs was enhanced by increasing the incubation temperature, the maximum being reached after 20-30 min at 37 degrees C. After 2.5 min at 65 degrees C, binding sites were completely destroyed. The same temperature-induced "activation" was obtained also by prewarming the cytosol at 37 degrees C in the absence of ligands.
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PMID:Polycyclic aromatic hydrocarbon binding macromolecules. Identification, characterization and temperature activation of a 4.5 S binding nucleoprotein. 406 Feb 44

Evidence is presented indicating that the chemically transformed AKR-MCA and C3H/MCA-58 murine cell lines produce "transforming growth factor(s)" capable of inducing a transformed morphology and the ability to grow in soft agar in nontransformed, anchorage-dependent indicator cells. Serum-free medium conditioned by exposure to the chemically transformed cells was chromatographed on a Bio-Gel P-60 column after dialysis and lyophilization. Using the nontransformed mouse AKR-2B cells as the indicator cells, a peak of soft agar growth-stimulating activity was detected in the molecular weight range of 10,000 to 12,000. The soft agar growth-stimulating activity in pooled fractions from the AKR-MCA cells was shown to be trypsin and dithiothreitol sensitive and relatively heat stable; the activity was not destroyed by heating to 56 degrees for 30 min or to 100 degrees for 3 min. The pooled material also caused stimulation of growth in the soft agar of rat NRK cells and stimulation of DNA synthesis in the AKR-2B cells. The quantity required to give significant competition for binding to the epidermal growth factor receptor was about one order of magnitude greater than that required for stimulation of soft agar growth. Further separation of these polypeptide(s) by carboxymethylcellulose chromatography revealed three apparent peaks of soft agar growth-stimulating activity. Epidermal growth factor receptor-competing activity cochromatographed with the early minor soft agar growth-stimulating peak, whereas the two major peaks of soft agar growth-stimulating activity had no associated detectable competition for epidermal growth factor binding to its receptor. The data indicate that at least a major portion of the transforming growth factors produced by the chemically transformed cells is different from those described previously in murine sarcoma virus-transformed mouse cells and human tumor cells.
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PMID:Transforming growth factor production by chemically transformed cells. 626 69

A tumor-derived suppressor factor ( TDSF ) has been isolated from 3 M KCl extracts of a chemically induced fibrosarcoma of C3H/HeJ mice by preparative isoelectric focusing. Incubation of TDSF with normal spleen cells induces suppressor cells that enhance tumor growth and inhibit DTH to the chemical sensitizer 2,4-dinitro-1-chlorobenzene (DNCB). Similar suppressogenic activity has been detected in extracts of the 10T1/2 fibroblast line, an ultraviolet-induced fibrosarcoma of C3H/HeN mice, the C57B1/6J Lewis lung carcinoma, and four human colonic adenocarcinoma. TDSF activity was not found in extracts of syngeneic muscle or spleen cells. Chemical characterization of TDSF from the murine fibrosarcoma MCA-F revealed sensitivity to treatment with heat and RNase, partial sensitivity to treatment with trypsin, but resistance to treatment with DNase, pronase, and neuraminidase. TDSF has an apparent molecular weight of greater than 300 kDa by high-performance gel permeation chromatography. Acidic soluble factors isolated from murine and human tumors induce suppressor cells to inhibit cell-mediated immunity in an intact host.
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PMID:Soluble factors from murine and human tumors induce suppressor cells. 653 7

Alterations in cell-cell interactions induced by urea and urea-isolated cell-surface protein (CSP) were examined using the nontumorigenic mouse fibroblast 10T1/2 cell line and the malignantly transformed MCA daughter cell line as a model system. Both cell lines were exposed to urea and CSP, and contact inhibition was quantitated based on nuclear overlaps. The Abercrombie Overlap index was found to be dependent on cell density, and a new method of overlap analysis was developed based on the regression of the number of overlaps per microscope field on the number of cells per field. Urea had a differential effect on both protein and deoxyribonucleic acid synthesis and a differential effect on the overlap regression in the two cell lines. Urea increased the regression coefficient in the normal (10T1/2) cell line while decreasing it in the transformed (MCA) cell line to approximately equal levels of overlap. Added CSP had no effects on overlaps in the MCA line but increased overlaps in the 10T1/2 line to the level of the MCA control, suggesting that the CSP interactions were more specific than the urea interactions. Trypsin-derived cell-surface glycopeptide profiles of the two cell lines showed a difference consistent with previously reported differences between normal and transformed cell lines. However, the glycopeptide profile of the urea-isolated CSP from the normal 10T1/2 cell line and the trypsin-derived glycopeptides of the transformed MCA cell line were not significantly different in the high-molecular-weight region, suggesting that the relative abundance of CSP may be higher in the MCA line, and the fact that the addition of CSP to the 10T1/2 line increased overlap tendency to the level of the MCA line suggested that CSP is an important factor in the modulation of overlap tendency. Urea and CSP may exert their effects on overlap tendency by affecting the integrity or order of the cell-surface components. The increased overlap tendency of the 10T1/2 line in the presence of CSP was not associated with increased cell density. Density dependence of cell growth was apparently not directly related to density dependence of overlap tendency. Many xenobiotics have surface-active properties and are known to inhibit protein synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The influence of urea and cell-surface protein on the behavior of nontumorigenic and chemically transformed cells. 662 Apr 11

3-Methylcholanthrene-induced tumor was challenged with a low molecular synthetic protease inhibitor, [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate. This drug at a dosage of 10 mg/kg or 20 mg/kg was administered by ip injection to 20 mice each harboring a solitary tumor twice daily for 10 weeks. This protease inhibitor significantly inhibited tumor growth and prolonged the survival time of the tumor-bearing mice (P less than 0.001). The results suggest the involvement of kinin-forming proteases, such as trypsin, plasmin and kallikrein, in the tumor growth.
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PMID:Inhibition of growth of 3-methylcholanthrene-induced mouse skin tumor by protease inhibitor [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate. 734 42

Two kinds of proteinases, type-I and type-II, were purified or partially purified from salted muscle of anchovy, Engraulis japonica. Mol. wts. of type-I and type-II proteinases were estimated to 25,000 and 37,000, respectively, on electrophoretic analysis. Both proteinases strongly hydrolyzed synthetic tri or tetrapeptide substrates specific to trypsin, alpha-thrombin, and an activated protein C, while they hardly hydrolyzed Arg-MCA and benzoyl Arg-MCA derivatives. The proteinases were inhibited by common trypsin inhibitors. Optimal pH for the proteinase activities were pH 6.8 (type-I) and pH 7.0 to 7.5 (type-II), and the proteinases showed the highest activities at 45 degrees C (type-I) and 50 degrees C (type-II). The N-terminal amino acid sequence of type-I proteinase, 1I-2V-3G-4G ... (29 residues were identified), was significantly similar to sequences of trypsins and tryptases. Based on these findings, both proteinases were presumed to be kinds of tryptases in E. japonica muscle.
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PMID:Two kinds of neutral serine proteinases in salted muscle of anchovy, Engraulis japonica. 761 98


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