Drupin, a thrombin‐like protease prompts platelet activation and aggregation through protease‐activated receptors
| Autor: | Amog P. Urs, Rajesh Rajaiah, Vilas Hiremath, Gotravalli V. Rudresha, Krishnegowda Jayachandra, Mallanayakanakatte D. Milan Gowda, Bannikuppe S. Vishwanath, Vaddarahally N. Manjuprasanna |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Platelets
Male 0301 basic medicine Proteases Platelet Aggregation medicine.medical_treatment Biochemistry Mice 03 medical and health sciences Thromboxane A2 chemistry.chemical_compound 0302 clinical medicine medicine Animals Platelet Platelet activation Molecular Biology Plant Proteins Protease Cell Biology Ficus Cysteine protease Cell biology 030104 developmental biology chemistry Coagulation 030220 oncology & carcinogenesis Hemostasis Receptors Thrombin Peptide Hydrolases Signal Transduction |
| Zdroj: | Journal of Cellular Biochemistry. 122:870-881 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | Hemostasis is a proteolytically regulated process that requires activation of platelets and the blood coagulation cascade upon vascular injury. Activated platelets create a thrombogenic environment and amplify the coagulation process. Plant latex proteases (PLPs) have been used as therapeutic components to treat various ailments by folk healers. One of the main applications of plant latices is to stop bleeding from minor injuries and to enhance wound healing activity. Although many studies have reported the pro-coagulant activities of PLPs, an in-depth investigation is required to understand the mechanism of action of PLPs on platelets. Here, the effect of PLPs on platelet aggregation was studied systematically to validate the observed pharmacological effect by folk healers. Among 29 latices from the Ficus genus tested, Ficus drupacea exhibited potent pro-coagulant and thrombin-like activity. Drupin, a thrombin-like cysteine protease responsible for platelet aggregation was purified from F. drupacea latex. Drupin exhibits pro-coagulant activity and reduces the bleeding time in mice tail. It induces platelet aggregation by activating mitogen-activated protein kinases and the nuclear factor-κB and PI3K/Akt signalling cascade, which, in turn, phosphorylats, cytosolic phospholipase A2 leading to the release of thromboxane A2 from the granules to activate the nearby platelets to aggregate. Furthermore, we investigated the involvement of protease-activated receptors in drupin-induced platelet aggregation using specific protease activated receptor 1 (PAR1) and PAR4 receptor antagonists. The results confirmed that the drupin-induced platelet aggregation was mediated by both PAR1 and PAR4, synergistically. Overall, drupin reduces the bleeding time by exerting pro-coagulant activity and induces platelet aggregation by activating the intracellular signalling cascade. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text