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

The inhibitory effect of thermo- and acid-resistant inhibitor of trypsin, chymotrypsin and leukocyte proteinases (TASPI) from rabbit serum on the kininogenase activity of cathepsins D from different organs and tissues (human spleen and liver, chicken liver, spleen leukemic infiltrate from patients with myeloid leukemia) was revealed. The progressive mechanism of TASPI and cathepsins D complexation dependent on time and temperature was revealed. The rate constant of inhibition (ki) of chicken liver cathepsin D by TASPI at 37 degrees was 4,25.10(3)M-1 min-1. It was shown that the kininogenase activity of chicken liver cathepsin D was slightly inhibited by the basic pancreatic trypsin and kallikrein inhibitor from bovine organs (Kunitz type) and by soya bean trypsin inhibitor. The role of TASPI as regulator of cathepsins D activity under pathological conditions accompanied by lysosomal disintegration is discussed.
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PMID:[Inhibition of kininogenase activity of cathepsins D by acid-resistant proteinase inhibitor from rabbit serum]. 691 92

Leukotoxin is a protein that is secreted by Aggregatibacter actinomycetemcomitans and that primarily targets the active form of leukocyte function associated antigen 1 (LFA1) on WBC. Because of its specificity for WBC, leukotoxin is being developed as a novel biologic treatment for hematologic malignancies and autoimmune-inflammatory diseases. Early studies indicated that leukotoxin is specific for WBC from humans and Old World primates. In the current study, we used in vivo and in vitro assays to show that leukotoxin has a wider host range than previously believed and can kill rodent WBC. Administration of leukotoxin to rats and mice resulted in a rapid drop in WBC number but had no effect on RBC or platelet counts. Using LFA1-knockout mice, we showed that leukotoxin-mediated depletion of WBC is dependent on LFA1. In addition, similar to its effect on human monocytes, leukotoxin kills murine myeloid leukemia via a lysosome-mediated pathway that is dependent on cathepsin D. This newly described broader host range of leukotoxin enables the biology of the protein to be studied in rodent species and offers the possibility of using rodent models for evaluating the therapeutic efficacy of leukotoxin in various diseases.
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PMID:Leukotoxin kills rodent WBC by targeting leukocyte function associated antigen 1. 2420 68