Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We cloned a previously characterized glioblastoma-derived parent cell line (12-18) in order to obtain a relatively homogenous population of human neural cells of neoplastic origin. These cells reach high densities in culture (over 100,000 cells/cm2) and have a high mean DNA content per cell of 18.1 +/- 0.9 pg. A histogram of the cloned cells' chromosome numbers revealed one peak and a modal near diploid number of 52, whereas the parent cell line had expressed polyploidy, with several peaks (including 52) at population doubling level 16. Several consistent results were obtained by Giemsa staining. A persistent structural alteration was the duplication of the long arm of chromosome #9 on to another arm of #9, and the translocation of the short arm of #9 to chromosome #21. We further observed that these cloned cells secrete a specific protease, a plasminogen activator (PA), into serum-free medium (SFM). This enzyme was assayed by the conversion of purified plasminogen to plasmin and the subsequent degradation by plasmin of 125I-labelled fibrin. Glioblastoma-derived cells had higher levels of cell-associated PA activity (2.9-fold) and released more PA activity into SFM (22-fold) than human fetal neural cells. The presence of this protease suggests a mechanism for the invasive character of these neoplasms (glioblastoma multiforme) in vivo.
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PMID:Properties of cloned human glioblastoma cells. Release of a specific protease. 676 10

The plasminogen-plasmin system has been found to modulate neoplastic spread and angiogenesis in tumors outside the central nervous system (CNS), but there have been no quantitative studies on the invasive and vascular tumors of the CNS. Quantitative zymography and enzyme-linked immunosorbent assay were used to determine the amounts of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator, and plasminogen activator inhibitors type 1 and type 2 (PAI-1 and PAI-2) in benign and malignant primary brain tumors (n = 28) as well as nonneoplastic brain (n = 5). u-PA and PAI-1 antigen were undetectable in normal brain but significantly elevated in glioblastoma multiforme (u-PA, 2.86 +/- 3.01 ng/mg; PAI-1, 8.19 +/- 5.57 ng/mg; P < 0.001). There was no difference, however, in tissue-type plasminogen activator antigen levels among control, benign, or malignant tissues except for a 4- to 7-fold increase in acoustic neuroma. PAI-2 was detected at low levels in 2 of the 33 specimens. These findings indicate that malignancy in primary CNS neoplasms is associated with elevated levels of u-PA and PAI-1, supporting the role of the plasminogen-plasmin system in the pathogenesis of CNS malignancy and as a potential biomarker and therapeutic target.
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PMID:Elevated levels of urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 in malignant human brain tumors. 831 68

We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs epsilon-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O2- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O2- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.
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PMID:Mechanism of antinephritic effect of proteinase inhibitors in experimental anti-GBM glomerulopathy. 1081 58