Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent work we have shown that a serine proteinase, stratum corneum chymotryptic enzyme, with properties compatible with a role in desquamation in vitro as well as in vivo, is generally present in human stratum corneum. The enzymologic properties of the stratum corneum chymotryptic enzyme in a KCl extract of dissociated plantar corneocytes were compared with those of other known chymotryptic serine proteinases. Stratum corneum chymotryptic enzyme was found to differ significantly from bovine chymotrypsin, human cathepsin G, and human mast cell chymases in regard to inhibitor profile and substrate specificity. Stratum corneum chymotryptic enzyme was further purified from KCl extracts of dissociated plantar corneocytes by affinity chromatography on gels with covalently linked soybean trypsin inhibitor. The purified preparation contained one major component with apparent molecular weight 25 kD and one minor component with slightly higher apparent molecular weight as revealed by Coomassie staining after electrophoresis in polyacrylamide gels with sodium dodecyl sulphate of samples that had not been reduced. Both these components were associated with chymotrypsin-like activity as revealed by zymography in polyacrylamide gels with co-polymerized casein. On zymography gels, the purified preparation was also found to contain minor amounts of components with trypsin-like activity. The major purified protein had an apparent molecular weight of around 28 kD after reduction and full denaturation and was shown to contain carbohydrate.
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PMID:Purification and preliminary characterization of stratum corneum chymotryptic enzyme: a proteinase that may be involved in desquamation. 839 2

Even though the skin surface is acidic (about pH 5), most in vitro studies on desquamation have been performed at alkaline pH. We demonstrate that the standard in vitro model system, which achieves squame shedding upon incubation of plantar stratum corneum for 1 day in an alkaline buffer that must include a chelating agent, can be extended to a more realistic model in which the incubation is for 4 days, at varying pHs from 5 to 8, without exogenous chelators. Desmoglein I from stratum corneum was degraded by the squames shed at pH 5 as well as at pH 8. Squame shedding was inhibited to varying extents by the addition of proteinase inhibitors, whose specificity suggested that the crucial enzymatic activity at pH 8 was a chymotrypsin-like serine proteinase, while a similar activity at pH 5 was accompanied by an aspartic proteinase activity of comparable strength. Four degradation peaks were observed when the insulin B chain was reacted with shed squames at pH 5. Two of these peptides were suppressed by the addition of phenylmethylsulphonyl fluoride, the other two by pepstatin A; chymostatin inhibited all four, but E-64 and leupeptin showed no effect. The implied specificity was confirmed by reacting the insulin (without squames) with the standard enzymes human liver cathepsin D and pancreatic chymotrypsin, reproducing the expected degradation products. These results suggest that epidermal desquamation at acidic pH requires two proteolytic activities, one of which is an analogue of chymotrypsin and the other of cathepsin D. Endogenous proteinases corresponding to these activities have been previously identified, namely the stratum corneum chymotryptic enzyme and the mature active form of cathepsin D.
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PMID:Role of endogenous cathepsin D-like and chymotrypsin-like proteolysis in human epidermal desquamation. 1058 48

Exposure to a dry environment leads to depletion of water from the peripheral stratum corneum layers in a process dependent on the relative humidity (RH) and the intrinsic properties of the tissue. We hypothesized that by modulating the water content of the stratum corneum in the surface layers, RH effects the rate of desquamation by modulating the activity of the desquamatory enzymes, and specifically stratum corneum chymotryptic enzyme (SCCE). Using a novel air interface in vitro desquamatory model, we demonstrated RH-dependent corneocyte release with desquamatory rates decreasing below 80% RH. Application of 10% glycerol or a glycerol-containing moisturizing lotion further increased desquamation, even in humid conditions, demonstrating that water was the rate-limiting factor in the final stages of desquamation. Furthermore, even in humid conditions desquamation was sub-maximal. In situ stratum corneum SCCE activity showed a dependence on RH: activity was significantly higher at 100% than at 44% RH. Further increases in SCCE activity were induced by applying a 10% glycerol solution. Since SCCE, a water-requiring enzyme, must function in the water-depleted outer stratum corneum, we sought to determine whether this enzyme has a tolerance to lowered water activity. Using concentrated sucrose solutions to lower water activity, we analysed the activity of recombinant SCCE and compared it to that of trypsin and chymotrypsin. SCCE activity demonstrated a tolerance to water restriction, and this may be an adaptation to maintain enzyme activity even within the water-depleted stratum corneum intercellular space. Overall these findings support the concept that in the upper stratum corneum, RH modulates desquamation by its effect upon SCCE activity, and possibly other desquamatory hydrolases. In addition, SCCE may be adapted to function in the water-restricted stratum corneum intercellular space.
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PMID:Water modulation of stratum corneum chymotryptic enzyme activity and desquamation. 1175 90