Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low molecular weight urokinase (LMW-UK) was coupled to the heavy chain of plasmin to make it able to bind to fibrin. The purified conjugate (PHC-UK conjugate), which consisted of equimolar concentrations of each starting material had a molecular weight of 93,600, bound tightly to fibrin-monomer-Sepharose and was not washed off with 1 M NaCl, but was eluted specifically with epsilon-amino caproic acid. The conjugate showed higher fibrinolytic activity than HMW-UK. A control conjugate prepared by coupling human serum albumin to LMW-UK (HSA-UK conjugate) showed the same fibrinolytic activity as HMW-UK. The half-lives of these two conjugates in rabbits were about 3 times that of HMW-UK. In an experimental pulmonary embolism model in rabbits, the PHC-UK conjugate showed about 10 times higher thrombolytic activity than HMW-UK, while the HSA-UK conjugate showed similar thrombolytic activity as HMW-UK, and moreover caused severe systemic fibrinogen breakdown. Thus the significant increase in thrombolytic activity after injection of PHC-UK conjugate into rabbits may be due to its newly acquired fibrin binding activity, and not to increase in its half-life. It is concluded that the PHC-UK conjugate may be useful in treatment of thrombosis.
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PMID:The plasmin heavy chain-urokinase conjugate: a specific thrombolytic agent. 295 92

Receptor-bound urokinase is likely to be a crucial determinant in both tumor invasion and angiogenesis. We report here that a yeast-derived genetic conjugate between human serum albumin and the 1-135 N-terminal residues of urokinase (u-PA) competitively inhibits the binding of exogenous and endogenous u-PA to its cell-anchored receptor (u-PAR). This hybrid molecule (ATF-HSA) also inhibits in vitro pro-urokinase-dependent plasminogen activation in the presence of u-PAR bearing cells. These effects are probably responsible for the observed in vitro inhibition of tumor cell invasion in a reconstituted basement membrane extract (Matrigel).
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PMID:Blockage of the urokinase receptor on the cell surface: construction and characterization of a hybrid protein consisting of the N-terminal fragment of human urokinase and human albumin. 798 21

The binding of urokinase (u-PA) to its cell surface receptor (u-PAR) is critical for tumor cell invasion. Here, we report that the distribution of this binding by a u-PAR antagonist ATF-HSA inhibits in vitro the motility of endothelial cells in a dose-dependent manner. This inhibition was also observed when the cells were first stimulated with potent angiogenic factors, including bFGF or VEGF. [3H]thymidine incorporation assay demonstrated that ATF-HSA did not affect the cell proliferation. ATF-HSA was more potent than plasmin inhibitors, suggesting that it exerts its effects not solely by inhibiting the remodeling of the extracellular matrix. In fact, analysis of the cell shape change during migration revealed for the first time that its effect is related to a decrease in cell deformability. These results suggest that u-PAR antagonist may be a new approach to control angiogenesis.
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PMID:Blockage of urokinase receptor reduces in vitro the motility and the deformability of endothelial cells. 860 39