Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrin(ogen) is important for hemostasis and is cleared from sites of vascular injury primarily by the plasminogen activator system. However, there is emerging evidence in plasminogen activator-deficient transgenic mice that non-plasmin pathways may also be important for endogenous fibrinolysis. We have recently described an alternative, plasmin-independent fibrinolytic pathway in activated human monocytes that utilizes the integrin Mac-1 (CD11b/CD18), which directly binds and internalizes fibrin, resulting in its lysosomal degradation. The identity of the lysosomal fibrinolytic enzyme(s) responsible for monocyte/macrophage-mediated fibrinolytic is unknown. Protease inhibitor studies now suggest that an aspartyl protease is responsible for this fibrinolytic activity. We, therefore, examined the fibrinolytic properties of cathepsin D, a lysosomal aspartyl protease, and report that cathepsin D possesses both fibrinogenolytic and fibrinolytic activity. Cathepsin D cleavage of fibrinogen follows Michaelis-Menten kinetics with a Michaelis constant, Km, of 1.5 microM; catalytic rate constant, kcat, of 1.4 x 10(-3) s-1; and catalytic efficiency, kcat/Km, of 9.3 x 10(-4) microM-1 s-1. A pH-activity profile of fibrinogen digestion by cathepsin D demonstrates a pH optimum of 3.5 with 50% residual activity at pH 5.0. Fibrinolysis was assessed by fibrin plate and fibrin clot lysis assays. Cathepsin D possesses significant fibrinolytic activity over a dose range of 100 nM to 10 microM and is able to lyse fibrin, as well as albumin-enriched and albumin/red cell-enriched fibrin clots. Cathepsin D cleaves the alpha-, beta-, and gamma-chains of FGN, generating multiple low-molecular-weight fragments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The fibrin(ogen)olytic properties of cathepsin D. 820 91

The monocyte/macrophage plays a central role in fibrinolysis. Cell-surface of components of the plasminogen activator system leads to the elaboration of plasmin, which facilitates degradation of fibrin in the pericellular environment, as well as activation of matrixins, which promote degradation of matrix components. Fibrin degradation also occurs by way of a proteolytic system within the macrophage lysosome that does not involve plasmin. This alternate pathway involves first the binding of fibrin(ogen) to the surface integrin Mac-1 (CD11b/CD18) followed by internalization of the complex into the lysosome where the aspartyl protease cathepsin D degrades the protein. These molecular events underlie the many physiologic and pathophysiologic processes in which the monocyte/macrophage is involved, including adhesion, migration, matrix degradation and remodeling, wound healing, fibrinolysis, and atherosclerosis.
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PMID:The macrophage and fibrinolysis. 912 15

The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear particle-induced and septic loosening and to gather new insights into the pathogenesis of endoprosthesis loosening. Gene expression profiles were generated from five periprosthetic membranes of wear particle-induced and five of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes were validated by RT-PCR (n = 30). The enzyme activity and the genotype of chitinase-1 were assessed in serum samples from 313 consecutive patients hospitalized for endoprosthesis loosening (n = 54) or for other reasons, serving as control subjects (n = 259). Eight hundred twenty-four genes were differentially expressed with a fold change greater than 2 (data sets on http://www.ncbi.nlm.nih.gov/geo/ GSE 7103). Among these were chitinase 1, CD52, calpain 3, apolipoprotein, CD18, lysyl oxidase, cathepsin D, E-cadherin, VE-cadherin, nidogen, angiopoietin 1, and thrombospondin 2. Their differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear particle-induced prosthesis loosening (p = 0.001). However, chitinase activity as a marker for early diagnosis has a specificity of 83% and a sensitivity of 52%, due to a high variability both in the disease and in the control group.
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PMID:Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis? 1790 71