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)

Abrin B chain and trypsin inhibitor isolated from Acacia confusa (ACTI) were covalently linked to form a chimeric protein (ANB-ACTI) with N-succinimidyl-3-(-2-pyridyldithio)propionate. The chimeric protein had 31% of trypsin inhibitory activity of ACTI and 7% of hemagglutinating activity of abrin B chain, but no inhibition on protein biosynthesis. ANB-ACTI had strong inhibitory effects on the growth of sarcoma 180 cells and Hela cell culture while the mixture of an equivalent amount of free abrin B chain and ACTI did not. The results suggests that abrin B chain of chimeric protein may act as a vector to carry ACTI into the tumor cells. ACTI into the tumor cells. ACTI in the chimeric protein potentiates its antitumor activity as well as its resistance to tryptic digestion.
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PMID:Chimeric protein: abrin B chain-trypsin inhibitor conjugate as a new antitumor agent. 281 99

A thiol proteinase inhibitor (TPI) has been purified from the ascitic fluid of Sarcoma 180 tumor-bearing mice. The molecular weight of the inhibitor was estimated to be 67,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the substance inhibited papain, cathepsins B and L, but not cathepsins H and D and trypsin. The inhibitor also liberated kinin upon treatment with trypsin or mouse glandular kallikrein, indicating that the inhibitor is a kininogen, and the kinin liberated upon trypsinization was identified as bradykinin. An immunoreactive TPI with a molecular weight indistinguishable from that of the ascites TPI was found in plasma of non-tumor-bearing mice as well as that of tumor bearers. Plasma levels of immunoreactivity were increased up to twice the normal levels in tumor bearers inoculated with Sarcoma 180 or 3LL tumor cells. Supplementation of the purified ascites TPI into Sarcoma 180 culture medium caused a significant suppression of cell growth as well as [3H]thymidine incorporation at a concentration below that normally present in plasma. In contrast, addition of ascites-TPI to cultured mouse embryonic cells caused enhancement of cell growth as well as [3H]thymidine incorporation. These results indicate that in mice responding to tumor growth, a TPI corresponding to a kininogen is induced which may regulate tumor growth by countering tumor-related proteolytic activity.
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PMID:Thiol proteinase inhibitor in the ascitic fluid of sarcoma 180 tumor-bearing mice. 366 64

Concanavalin A (Con A) and trypsin inhibitor isolated from Acacia confusa were covalently linked with N-succinimidyl-3-(2-pyridyldithio)propionate. Con A-A. confusa trypsin inhibitor (ACTI) conjugate covalently bound (Con A-ACTI) retained about 42% of the trypsin inhibitory activity present in the native ACTI and had a higher hemagglutinating activity than did the native Con A. Con A-ACTI had a greater resistance to tryptic digestion than did the mixture of Con A and ACTI. The conjugate entered sarcoma 180 tumor cells, whereas the free ACTI did not. A single dose of the conjugate injected ip into noninbred N:NIH(S) white mice bearing sarcoma 180 had a remarkable effect of increasing the survival of tumor-bearing mice, while the mixture of an equivalent dose of free Con A and ACTI was not effective.
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PMID:Antitumor lectin-trypsin inhibitor conjugate. 388 55

A supernatant factor derived from monodispersed bone marrow cells was tested for its ability to inhibit the growth of tumor cell lines and freshly dispersed hemopoietic cells in vitro. The supernatant fluid from bone marrow cells was capable of inhibiting the mitogenic response of rat thymocytes to concanavalin A. It also was capable of inhibiting growth of HeLa cells, Sarcoma 180, EL-4, and BALB/c K3T3 tumor cell lines as measured by thymidine incorporation. The factor did not inhibit the growth of normal thymus cells, marrow cells, or WI-38-SV40, and F-46 tumor cell lines. From data derived from 51Cr release assays, the factor appears to be selectively cytoreductive. Bone marrow supernatant factor is stable to heat (100 degrees for 10 min) and trypsin digestion, but is sensitive to carboxypeptidase B digestion. Molecular weight estimation by gel filtration chromatography on a Sephadex G-75 column indicates its apparent molecular weight to be less than 12,000. Bone marrow supernatant factor appears to function across species and strain barriers.
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PMID:Suppression of tumor cell growth in vitro by a bone marrow factor. 669 11

We have used photoaffinity labeling to investigate the distribution and function of daunomycin binding sites in Sarcoma 180 cells. When native daunomycin is irradiated at 366 or 488 nm in the presence of cells, the drug is irreversibly incorporated into cellular molecules. The cellular acceptor for the photoincorporation cannot be extracted by chloroform-methanol nor can it be degraded by DNase. However, the drug acceptor is susceptible to trypsin digestion. These results show that the photoincorporation site is composed of protein but not of lipid or DNA. Furthermore, the fact that photoincorporation proceeds equally well at 0 degrees (where drug does not accumulate inside the cells) as compared to 37 degrees (where free drug concentrates in the cells) suggests that the labeling reaction occurs principally at the cell surface. The photolabeling process is not highly specific since it is not saturable at high drug concentrations and cannot be competed for by unlabeled daunomycin. When 2 X 10(5) daunomycin molecules are incorporated per Sarcoma 180 cell, the cells can still accumulate free drug. This result suggests that the photolabeling reaction does not occur at the drug transport locus. Photoincorporation of daunomycin also does not affect the viability of Sarcoma 180 cells, as judged by a cloning assay. Thus, there is probably no surface receptor for the drug which mediates cytotoxicity when occupied. This result is as expected from previous work predicting that the mechanism of daunomycin involves disruption of some generalized membrane property like fluidity. However, in a series of Sarcoma 180 sublines selected for increasing resistance to daunomycin, the photoincorporation increases in direct proportion to drug sensitivity. Consequently, daunomycin appears to be capable of photoaffinity labeling a cell surface protein which, although not directly involved in the mechanism of cytotoxicity is implicated in the expression of drug resistance.
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PMID:Photoaffinity labeling of the Sarcoma 180 cell surface by daunomycin. 671 90

The windowpane flounder, Lophopsetta maculata, was found to have proteins in the body mucus which agglutinate mouse leukemia cells, L5784Y but not L1210. They also agglutinate rabbit and mouse erythrocytes, a marine yeast and a bacterium, and have weak activity against mouse sarcoma 180 cells, human B, guinea pig, and horse erythrocytes. The hemagglutinating activity was not affected by the treatment with 2-mercaptoethanol, trypsin, or pronase, but was inhibited by a high concentration of N-acetylneuraminic acid. The major active component was purified and found to be a protein having a molecular weight of 68 000 which dissociates into subunits of equal size (16 000). Isoelectrofocusing gave two sharp bands, close together, at pI 4.7 +/- 0.1. The protein contains high amounts of aspartic acid, glutamic acid and glycine, and very little histidine and half-cystine.
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PMID:Marine biopolymers with cell specificity. II. Purification and characterization of agglutinins from mucus of windowpane flounder Lophopsetta maculata. 737 46

A lipolytic substance in the ascites fluid of mice with Sarcoma 180, called toxohormone-L, was purified and characterized. The lipolytic activity of toxohormone-L was measured in vitro using rat adipose tissue slices. Toxohormone-L, purified approximately 90-fold from the ammonium sulfate fraction, gave a single band on polyacrylamide gel electrophoresis. Its molecular weight was about 75,000, and its isoelectric point was 4.7. Toxohormone-L is heat labile and nondialyzable, but, on its digestion with trypsin, an active fragment that was heat stable and dialyzable was produced. Toxohormone-L is a protein and is also present in the ascites fluid of patients with hepatoma and Grawitz's tumor.
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PMID:Purification and characterization of a lipolytic factor (toxohormone-L) from cell-free fluid of ascites sarcoma 180. 744 67

In this study, using zymogram analysis two proteolytic activities were identified in the mouse sarcoma 180 (S-180) cells that were activated by trypsin treatment and inhibited by both BBI and ACTI. These enzymes, with molecular weights of 46 kDa (dominant band) and 62 kDa (minor band), were mainly localized in the cytosol, and had optimal activity at pH 7 and 8 respectively. Their inhibition by DFP, BBI and ACTI but not EDTA and TPCK indicated they were trypsin-like serine proteases and may be the intracellular target-enzymes of protease inhibitors. The level of the precursor of the 62 kDa protease was significantly increased in the S-180 solid and soft tumors, whereas the level of the 46 kDa precursor was almost undetectable, implying that a physiological role may be played by these serine proteases during tumor invasion.
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PMID:Proteolytic activities of mouse sarcoma 180 cells that are inhibited by Bowman-Birk and Kunitz protease inhibitors. 928 64