The effect of protamine sulfate upon the covalent interaction of human factor IXa with anti-thrombin has been investigated by a quantitative SDS-polyacrylamide gel electrophoresis procedure. Protamine sulfate inhibits the interaction of factor IXa with anti-thrombin upon preincubation with factor IXa, anti-thrombin, or a mixture of the two components. As a consequence of the presence of protamine sulfate, autolysis of factor IXa is promoted to generate a degradation product of a molecular weight (apparent) of 35 kDa. Concomitantly, free factor IXa and free anti-thrombin levels are increased in the mixture. In contrast to the effect of protamine sulfate, heparin promotes a massive increase in the factor IXa-anti-thrombin complex appearing as a doublet. Associated with the increase in the complex is a precipitous drop in free factor IXa and anti-thrombin, as well as the steep decline in the 35 kDa factor IX fragment, the presence of which reflects the degradation of factor IXa. Accordingly, protamine sulfate appears to exert a procoagulant effect upon addition to an intrinsic coagulation system enzyme, in contrast to its modest anticoagulant effect on the overall coagulation process.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/MBC.0b013e328308917c | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Expression Profiles of Brain-Derived Neurotrophic Factor Splice Variants in the Hippocampus of Alzheimer's Disease Model Mouse.
Biol Pharm Bull
November 2024
Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare.
Article Synopsis
- Dysregulation of BDNF is linked to Alzheimer's disease, and this study examined its expression in the hippocampus of 5xFAD mice, focusing on sex and age.
- At 3 months, female wild-type mice had higher Bdnf mRNA levels than males, but this difference disappeared in female 5xFAD mice.
- By 6 months, female 5xFAD mice showed a significant decrease in full-length TrkB receptor mRNA while increased levels of truncated TrkB were observed in both sexes, highlighting potential disruptions in BDNF signaling due to Alzheimer's.
- The research indicates that certain Bdnf splice variants are maintained at higher levels in young female mice but may be affected by Alzheimer's
Discovery of a new lead molecule to develop a novel class of human factor XIIa inhibitors.
J Thromb Thrombolysis
December 2024
Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, 70125, USA.
Article Synopsis
- FXIIa is a plasma protease in the contact activation pathway, and inhibiting it could lead to safer anticoagulation treatments without the bleeding risks of current options.!* -
- The study tested an amidine-containing molecule (inhibitor 1) and found it primarily inhibits human FXIIa with an IC value of ~30 µM, while showing variable selectivity against other factors involved in blood coagulation.!* -
- Inhibitor 1 effectively prolongs clotting time in plasma without significant cytotoxicity, making it a promising candidate for further development as a safer anticoagulant for thromboembolic diseases.!*
Docking-based computational analysis of guava () leaves derived bioactive compounds as a coagulation factor IXa inhibitor.
RSC Adv
August 2024
Department of Chemistry, Technological University of the Philippines Ayala Boulevard, Ermita Manila Philippines.
Thrombotic disorders pose a global health threat, emphasizing the urgent need for effective management strategies. This study explores the potential of bioactive compounds derived from guava leaves in inhibiting coagulation factor IXa (CFIXa) using methods. Using GC-MS, bioactive compounds extracted from guava leaf through ethanol maceration were identified.
View Article and Find Full Text PDFBlood coagulation factor IX: structural insights impacting hemophilia B therapy.
Blood
November 2024
Department of Medicine and UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Coagulation factor IX plays a central role in hemostasis through interaction with factor VIIIa to form a factor X-activating complex at the site of injury. The absence of factor IX activity results in the bleeding disorder hemophilia B. This absence of activity can arise either from a lack of circulating factor IX protein or mutations that decrease the activity of factor IX.
View Article and Find Full Text PDFAn RNA aptamer exploits exosite-dependent allostery to achieve specific inhibition of coagulation factor IXa.
Proc Natl Acad Sci U S A
July 2024
Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Hemostasis relies on a reaction network of serine proteases and their cofactors to form a blood clot. Coagulation factor IXa (protease) plays an essential role in hemostasis as evident from the bleeding disease associated with its absence. RNA aptamers specifically targeting individual coagulation factors have potential as anticoagulants and as probes of the relationship between structure and function.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!