Effects of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA.
Effects of heparan sulfate analogue (HHS-5) and other sulfated polysaccharides on the fibrinolytic system were investigated. Activation rate of native plasminogen (Glu-plg) by tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and single-chain u-PA (scu-PA) was enhanced in the presence of HHS-5 dose dependently up to 10 micrograms/ml. Activation rate of Glu-plg by sct-PA was more enhanced than that by tct-PA in its presence. HHS-5 enhanced the activation of Glu-plg by t-PA or u-PA compared to the activation of Lys-plg. SDS-PAGE confirmed that the enhancement of the hydrolysis of S-2251 by the mixture of Glu-plg, sct-PA and HHS-5 was due to the facilitation of the conversion of Glu-plg to plasmin. HHS-5 only slightly enhanced the amidolytic activity of sct-PA or tct-PA. The enhancement of the activation of plasminogen by t-PA or u-PA was more significant in the presence of HHS-5 than in the presence of chondroitin sulfate C, dextran sulfate or heparin. It is possible that the enhancement of the activation of Glu-plg by activators in the presence of HHS-5 was due to the conformational change of Glu-plg upon interaction with HHS-5.
Takada
Y
Y
Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka, Japan.
Urano
T
T
Takada
A
A
D002809:Chondroitin Sulfates / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005341:Fibrinolysin / Q000096:biosynthesis; D006497:Heparan Sulfate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000187:drug effects*; D010958:Plasminogen / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology*; D013268:Stimulation, Chemical; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D002809:Chondroitin Sulfates; D016264:Dextran Sulfate; D005341:Fibrinolysin; D006497:Heparan Sulfate; D010446:Peptide Fragments; D010958:Plasminogen; D011134:Polysaccharides; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C018998:lysyl-plasminogen; C087964:HHS 5