Tau aggregates into paired helical filaments within neurons, a pathological hallmark of Alzheimer's disease. Heparin promotes tau aggregation and recently has been shown to be involved in the cellular uptake of tau aggregates. Although the tau-heparin interaction has been extensively studied, little is known about the glycan determinants of this interaction. Here, we used surface plasmon resona...

Inactivation of plasmin by a 3-4-fold molar excess of antithrombin III follows pseudo-first-order kinetics and the apparent rate constants are proportional to the concentration of the inhibitor. Heparin accelerates the inactivation reaction without changing its pseudo-first-order character, and the apparent rate constants are also proportional to the concentration of the polysaccharide. Heparin...

Heparin binding to rabbit histidine-rich glycoprotein (HRG) was studied in a purified system, allowing for determination of a heparin dissociation constant of approximately 5.5 X 10(-8) M for the interaction with HRG at pH 7.0. The strong interaction between heparin and HRG was demonstrated to be competitive with the binding of both antithrombin and thrombin to the heparin chain. HRG was furthe...

The contribution of individual basic amino acids within three putative "consensus sequences" for heparin binding of fibroblast growth factor-1 have been examined by site-directed mutagenesis. The results indicate that a significant reduction in the apparent affinity of fibroblast growth factor-1 for heparin is only observed when basic residues in one of the three regions are mutated. Mutation i...

Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin compl...

Coronary thrombolysis with t-PA is generally implemented with concomitant administration of heparin. However, results of studies in vitro suggest that heparin competes with fibrin for binding of tissue-type plasminogen activator (t-PA), augments activation of free plasminogen, decreases fibrin specificity, and impairs thrombolysis. To define the biological implications of these observations, we...

The interference of the heparin-neutralizing plasma component S protein (vitronectin) (Mr = 78,000) with heparin-catalyzed inhibition of coagulation factor Xa by antithrombin I11 was investigated in plasma and in a purified system. In plasma, S protein effectively counteracted the anticoagulant activity of heparin, since factor Xa inhibition was markedly reduced in comparison to heparinized pla...

introduction deep vein thrombosis is one of the most important complications in patients with spinal cord injury. this study compares the effects of mechanical prophylaxis with or without pharmacological prophylaxis on prevention of deep vein thrombosis in patients with spinal cord injury. materials and methods we conducted a double blind clinical trial study with 75 cases. these patients were ...

An understanding of the substrate specificity study of the heparin lyases (heparinase and heparitinases) is crucial for elucidation of the sequence of heparin and heparan sulfate. Four chemically modified heparins have been used to study the substrate specificity of the three heparin lyases. These modified heparins include the N- and O-desulfated and then specifically N-sulfated or N-acetylated...

Heparin cofactor II and antithrombin are plasma serine proteinase inhibitors whose ability to inhibit alpha-thrombin is accelerated by glycosaminoglycans. Dysfunctional thrombin mutants Quick I (Arg67-->Cys) and Quick II (Gly226-->Val) were used to further compare heparin cofactor II and antithrombin interactions. Quick I, Quick II, and alpha-thrombin were eluted at the same salt concentration ...