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)

Ascites fluid accumulation accompanying a mastocytoma or L1210 murine tumor is significantly retarded following the i.p. or s.c. injection of moderate quantities of pepstatin, a known acid protease inhibitor. No effect on cell count was noted by pepstatin treatment. The probable mechanism by which pepstatin acts is by inhigiting the enzymatic formation of chemical mediators known as leukokinins. These are pharmoacologically active peptiedes having potent permeability characteristics previously described by this laboratory. Leukokinins are formed by cathepsin D-like enzymes present in the invading cells and in the ascites fluid acting on a protein substrate, leukokininogen. present in the ascites fluid. Pestatin inhibits the action of these leukokinin-forming enzymes invitro but has no effect on kallikreins (bradykinin-forming enzymes) in vitro. Human ascites fluid from a patient with ovarian carcioma was found to have a paepstatin-inhibited, leukokinin-generating system, as does the mouse. A 'chemical mediator' theory is proposed for ascites fromation which broadens the previously held theory of lymphatic blockage (Holm-Nielsen) and may explain the recent findings of Hirabayashi and Graham of increased plasma-ascites exchange in peritoneal carcionmatosis. Pepstatin inhibition of chemical mediator formation may represent a new therapeutic approach to ascites fluid accumulation in neoplastic disease.
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PMID:Pepstatin, an inhibitor of leukokinin formation and ascitic fluid accumulation. 4 79

Proliferation of mastocytoma P-815 cells in vitro was accompanied by a rise in cathepsin D, elastase- and trypsin-like proteinase activity during 6 hours of culturing and a decline by hour 24. Yet alpha 1-proteinase inhibitor activity was inversely proportional to proteinase concentration. Antiproliferative action of actinomycin D disrupted phase variation of proteinase activity and, consequently, the level of alpha 1-proteinase inhibitor rose after 6 hours of cell culturing while that of alpha 2-macroglobulin--after 48 hr. Antiproliferative effect of actinomycin D was eliminated by reduced inhibitor level brought about under the influence of exogenous trypsin. When trypsin was added cathepsin D activity reached its peak 6 hr later while that of alpha 1-proteinase inhibitor declined. That effect and the actomycin D-proteinase inhibitor mechanism were retained when trypsin and actomycin D were present together. It is suggested that cathepsin D and alpha 1-proteinase inhibitor activity plays a key role in realizing the proliferative potential of mastocytoma P-815 cells.
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PMID:[Activity of proteolytic enzymes and their inhibitors during proliferation of P-815 mastocytoma cell proliferation in vitro]. 1178 7