Disease relevance of Chymostatin

• By using synthetic peptidyl substrates, we have detected and characterized a chymostatin-sensitive peptidase activity in chicken embryo fibroblasts transformed by Rous sarcoma virus [1].
• Elastatinal (100 mg/kg body weight twice a day) and chymostatin (100 mg/kg body weight once a day) did not inhibit formation of metastatic foci of AH7974 cells [2].
• Chymostatin, a serine protease inhibitor that does not prevent the activation of NF-kappaB, had no effect on the organ injury/failure caused by hemorrhagic shock [3].
• Chymostatin inhibited the angiogenesis induced by Ang I but not Ang II, suggesting the presence of a chymase-like Ang II-generating activity in the sponge granulomas [4].
• Structure of the complex formed between the bacterial-produced inhibitor chymostatin and the serine enzyme Streptomyces griseus protease A [5].

Psychiatry related information on Chymostatin

• When 3-week-old dystrophic mice received chymostatin (1 mg/kg, i.p.), the decrease in locomotor activity was retarded, serum enzyme levels decreased significantly, and muscle protein content increased significantly [6].

High impact information on Chymostatin

• Chymostatin selectively inhibited the monocyte-derived plasminogen activators [7].
• Detection and partial characterization of a chymostatin-sensitive endopeptidase in transformed fibroblasts [1].
• Concurrent treatment with the protease inhibitor chymostatin completely prevents PrPc loss [8].
• These results suggest that the apparent induction of intracellular transglutaminase activity is mediated by a chymostatin-sensitive protease, while both phorbol ester binding and the reduction by TPA of epidermal growth factor binding at the cell membrane were independent [9].
• On the other hand, (30bp)DNA has little or no effect on the reversible inhibition of cat G by MPI or chymostatin or on the irreversible inhibition of cat G by carbobenzoxy-Gly-Leu-Phe-chloromethylketone [10].

Chemical compound and disease context of Chymostatin

• Neutral and acid protease activities inhibited by chymostatin, leupeptin, pepstatin and HgCl2 in mononuclear cells and granulocytes showed no significant differences between myotonic dystrophy patients and controls [11].
• In this study we evaluated in vitro the influence of four common protease inhibitors: aprotinin, phenylmethylsulphonyl fluoride (PMSF), l-1-chloro-3-[4-tosylamido]-7-amino-2-heptanone-HCl (TLCK) and chymostatin on the toxicity of C. histolyticum supernatant towards human epithelial HeLa cells [12].
• The effect of protease inhibitors obtained from the culture filtrates of actinomycetes (pepstatin, chymostatin, leupeptin, phosphoramidon and elastatinal) on the in vitro invasion of erythrocytes from rhesus and assamese monkeys by Plasmodium knowlesi merozoites was studied [13].
• The inhibitory effects of leupeptin and antipain were completely reversed by amino acid addition, whereas some inhibition remained in the case of chymostatin and the lysosomotropic amines, possibly reflecting a certain nonspecific toxicity [14].
• On the basis of experiments using amino acids and various inhibitors (lysosomotropic amines, leupeptin, chymostatin, vanadate, vinblastine, anoxia, methylaminopurines), five different modes of endogenous protein degradation in isolated rat hepatocytes can be distinguished [15].

Biological context of Chymostatin

• The response to chymase was non-cytotoxic and was blocked by active site inhibitors of chymase (soybean trypsin inhibitor and chymostatin) and by inhibitors of cellular energy metabolism (azide,2,4-dinitrophenol, dicumarol) [16].
• The peptide aldehydes, antipain and chymostatin, form covalent adducts with the active-site serine 146 [17].
• Inhibition kinetics indicate second-order rate constants for the association of chymostatin with chymotrypsin and cathepsin G of 360,000 and 2000 M-1 S-1, respectively and a first-order rate constant for the dissociation of both protease-chymostatin complexes of approximately 0.0002 s-1 [18].
• The proteinase is characterized by a broad substrate specificity, optimal activity at 35 to 40 degrees C (pH 8.0) in the presence of human collagen, elastin, or hemoglobin, an isoelectric point of pH 4.5, and inhibition by organofluorides, N-tosyl-L-phenylalanine chloromethyl ketone, chymostatin, and alpha-1-antitrypsin [19].
• The hydrolysis by SAM-P45 of the synthetic substrate (N-succinyl-L-Gly-L-Pro-L-Lys-p-nitroanilide) most preferred by this enzyme was inhibited by SSI, chymostatin, and EDTA [20].

Anatomical context of Chymostatin

• Evidence that the enzyme being released in the peritoneal cavity of rats was chymase was provided both by its appearance after adding specific mast cell activators (ie, compound 48/80 and anti-IgE [gamma E immunoglobulin]) and by inhibition with chymostatin [21].
• Chymostatin inhibited both the in vitro enzymatic activity and the processing of profilaggrin in a cultured rat keratinocyte cell line [22].
• When monocytes were preincubated with drugs for 1 hr and washed, TLCK, TPCK, and PMSF inhibited cytolysis, whereas the less effective chymostatin and TAME and the inactive BPTI had no effect under these conditions [23].
• The protease inhibitors leupeptin and chymostatin, which slowed overall proteolysis in nongrowing muscles and hepatocytes, reduced the degradation of the ACh receptor by 2--11-fold, but had no, or only slight, effects on the catabolism of average protein, even when overall proteolysis was accelerated by omitting serum and embryo extract [24].
• The effect of synthetic analogues of chymostatin upon protein degradation in isolated skeletal muscle [25].

Associations of Chymostatin with other chemical compounds

• Schizonts of Plasmodium falciparum were cultured in medium containing a mixture of 10 micrograms/ml each of leupeptin, chymostatin, pepstatin, and antipain [26].
• Using wire myography, concentration response curves to angiotensin I (AI) and AII were constructed in the presence of 1) vehicle, 2) chymostatin [an inhibitor of chymase], 3) enalaprilat, and 4) the combination of chymostatin and enalaprilat [27].
• Addition of the nonselective tryptase inhibitor antipain, the specific trypsinlike protease inhibitor 4-amidinophenylmethanesulfonyl fluoride, and the chymase inhibitor chymostatin reduced this increase in MMP activity by 30+/-6%, 23+/-6%, and 9+/-2%, respectively [28].
• Maximum activity with the first group of substrates was at pH 10.5, and this activity was inhibited by leupeptin, chymostatin and Ca2+ [29].
• A preliminary characterization of the secreted acid protease of Tetrahymena suggests that there may be two acid proteases released, since up to 25% of the activity was not inhibited by high concentrations of pepstatin, leupeptin, or chymostatin [30].

Gene context of Chymostatin

• 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 [31].
• IL-1-induced activation of pro-MMP-9 was inhibited by chymostatin, a chymotrypsinlike proteinase inhibitor [32].
• Unlike PD159790, chymostatin did not significantly modify the maximum response to big endothelin-1 [33].
• Our data suggest a role for both endothelin-converting enzyme and a chymostatin-sensitive enzyme, such as chymase, in the conversion of big endothelin-1 to constrictor endothelin peptides in human umbilical vein smooth muscle [33].
• The chymotryptic activity of PSA was further confirmed by the ability of alpha-1-antichymotrypsin and chymostatin to block PSA cleavage of radiolabeled IGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS)[34]

Analytical, diagnostic and therapeutic context of Chymostatin

• Chymostatin reversed ECP-mediated suppression of PHA-induced T-lymphocyte proliferation in separated cultures, but not in cocultures [35].
• Crystallization of fiber purified in the presence of chymostatin provided crystals of a different structure under the electron microscope (crystals of type II), composed of 62-kDa fiber polypeptide units [36].
• Affinity chromatography of chymotrypsin on a sepharose derivative coupled with a chymostatin analogue [37].
• This may make some contribution to the regulation of tissue perfusion, as seen in the ischemic dog heart and the human leg; and (2) chymostatin-sensitive or the chymase type which only forms angiotensin II and may participate in structural remodelling of heart and vessels rather than in tissue perfusion [38].

References