Effects of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA

Abstract

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 μg/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.